研究等業績 - 原著論文 - 石井　聡

Autotaxin–lysophosphatidic acid receptor 5 axis evokes endothelial dysfunction via reactive oxygen species signaling

Janovicz A., Majer A., Kosztelnik M., Geiszt M., Chun J., Ishii S., Tigyi G.J., Benyó Z., Ruisanchez É.

Experimental Biology and Medicine ( Experimental Biology and Medicine )  248   1887 - 1894   2023年10月  [査読有り]

研究論文（学術雑誌）   国際共著

Lysophosphatidylcholine (LPC) is a bioactive lipid that has been shown to attenuate endothelium-dependent vasorelaxation contributing to endothelial dysfunction; however, the underlying mechanisms are not well understood. In this study, we investigated the molecular mechanisms involved in the development of LPC-evoked impairment of endothelium-dependent vasorelaxation. In aortic rings isolated from wild-type (WT) mice, a 20-min exposure to LPC significantly reduced the acetylcholine chloride (ACh)–induced vasorelaxation indicating the impairment of normal endothelial function. Interestingly, pharmacological inhibition of autotaxin (ATX) by GLPG1690 partially reversed the endothelial dysfunction, suggesting that lysophosphatidic acid (LPA) derived from LPC may be involved in the effect. Therefore, the effect of LPC was also tested in aortic rings isolated from different LPA receptor knock-out (KO) mice. LPC evoked a marked reduction in ACh-dependent vasorelaxation in Lpar1, Lpar2, and Lpar4 KO, but its effect was significantly attenuated in Lpar5 KO vessels. Furthermore, addition of superoxide dismutase reduced the LPC-induced endothelial dysfunction in WT but not in the Lpar5 KO mice. In addition, LPC increased H₂O₂ release from WT vessels, which was significantly reduced in Lpar5 KO vessels. Our findings indicate that the ATX–LPA–LPA₅ receptor axis is involved in the development of LPC-induced impairment of endothelium-dependent vasorelaxation via LPA₅ receptor–mediated reactive oxygen species production. Taken together, in this study, we identified a new pathway contributing to the development of LPC-induced endothelial dysfunction.

DOI

Inverse agonism of lysophospholipids with cationic head groups at Gi-coupled receptor GPR82

Yasuda D., Hamano F., Masuda K., Dahlström M., Kobayashi D., Sato N., Hamakubo T., Shimizu T., Ishii S.

European Journal of Pharmacology ( European Journal of Pharmacology )  954   175893   2023年09月  [査読有り]

研究論文（学術雑誌）   国際共著

GPR82 is an orphan G protein-coupled receptor (GPCR) that has been implicated in lipid storage in mouse adipocytes. However, the intracellular signaling as well as the specific ligands of GPR82 remain unknown. GPR82 is closely related to GPR34, a GPCR for the bioactive lipid molecule lysophosphatidylserine. In this study, we screened a lipid library using GPR82-transfected cells to search for ligands that act on GPR82. By measuring cyclic adenosine monophosphate levels, we found that GPR82 is an apparently constitutively active GPCR that leads to Gi protein activation. In addition, edelfosine (1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine), an artificial lysophospholipid with a cationic head group that exerts antitumor activity, inhibited the Gi protein activation by GPR82. Two endogenous lysophospholipids with cationic head groups, lysophosphatidylcholine (1-oleoyl-sn-glycero-3-phosphocholine) and lysophosphatidylethanolamine (1-oleoyl-sn-glycero-3-phosphoethanolamine), also exhibited GPR82 inhibitory activity, albeit weaker than edelfosine. Förster resonance energy transfer imaging analysis consistently demonstrated that Gi protein-coupled GPR82 has an apparent constitutive activity that is edelfosine-sensitive. Consistent data were obtained from GPR82-mediated binding analysis of guanosine-5'-O-(3-thiotriphosphate) to cell membranes. Furthermore, in GPR82-transfected cells, edelfosine inhibited insulin-induced extracellular signal-regulated kinase activation, like compounds that function as inverse agonists at other GPCRs. Therefore, edelfosine is likely to act as an inverse agonist of GPR82. Finally, GPR82 expression inhibited adipocyte lipolysis, which was abrogated by edelfosine. Our findings suggested that the cationic lysophospholipids edelfosine, lysophosphatidylcholine and lysophosphatidylethanolamine are novel inverse agonists for Gi-coupled GPR82, which is apparently constitutively active, and has the potential to exert lipolytic effects through GPR82.

DOI PubMed

Lysophosphatidic acid signaling via LPA<inf>6</inf>: A negative modulator of developmental oligodendrocyte maturation

Spencer S.A., Suárez-Pozos E., Verdugo J.S., Wang H., Afshari F.S., Guo L., Manam S., Yasuda D., Ortega A., Lister J.A., Ishii S., Zhang Y., Fuss B.

Journal of Neurochemistry   163 ( 6 ) 478 - 499   2023年02月  [査読有り]

研究論文（学術雑誌）   国際共著

The developmental process of central nervous system (CNS) myelin sheath formation is characterized by well-coordinated cellular activities ultimately ensuring rapid and synchronized neural communication. During this process, myelinating CNS cells, namely oligodendrocytes (OLGs), undergo distinct steps of differentiation, whereby the progression of earlier maturation stages of OLGs represents a critical step toward the timely establishment of myelinated axonal circuits. Given the complexity of functional integration, it is not surprising that OLG maturation is controlled by a yet fully to be defined set of both negative and positive modulators. In this context, we provide here first evidence for a role of lysophosphatidic acid (LPA) signaling via the G protein-coupled receptor LPA6 as a negative modulatory regulator of myelination-associated gene expression in OLGs. More specifically, cell surface accessibility of LPA6 was found to be restricted to the earlier maturation stages of differentiating OLGs, and OLG maturation was found to occur precociously in Lpar6 knockout mice. To further substantiate these findings, a novel small molecule ligand with selectivity for preferentially LPA6 and LPA6 agonist characteristics was functionally characterized in vitro in primary cultures of rat OLGs and in vivo in the developing zebrafish. Utilizing this approach, a negative modulatory role of LPA6 signaling in OLG maturation could be corroborated. During development, such a functional role of LPA6 signaling likely serves to ensure timely coordination of circuit formation and myelination. Under pathological conditions as seen in the major human demyelinating disease multiple sclerosis (MS), however, persistent LPA6 expression and signaling in OLGs can be seen as an inhibitor of myelin repair. Thus, it is of interest that LPA6 protein levels appear elevated in MS brain samples, thereby suggesting that LPA6 signaling may represent a potential new druggable pathway suitable to promote myelin repair in MS.

DOI PubMed

Cell-trafficking impairment in disease-associated LPA6 missense mutants and a potential pharmacoperone therapy for autosomal recessive woolly hair/hypotrichosis.

Yanagida, K., Masago, K., Yasuda, D., Hamano, F., Kurikawa, Y., Shimizu, T. ,Ishii, S.

Human Molecular Genetics   32 ( 5 ) 825 - 834   2022年09月  [査読有り]

研究論文（学術雑誌）   国内共著

In human autosomal recessive woolly hair/hypotrichosis (ARWH/HT), many mutations have been identified in a gene encoding LPA6, a G protein-coupled receptor (GPCR) for lysophosphatidic acid (LPA). However, information regarding the effects of such mutations on receptor function is limited. In this study, we examined functional impacts of selected amino acid changes in LPA6 identified in ARWH/HT patients. In our exogenous expression experiments, all mutants except S3T failed to respond to LPA, indicating that they are loss-of-function mutants. Among the nine mutants, five (D63V, G146R, N246D, L277P, and C278Y) displayed impaired expression at the cell surface due to endoplasmic reticulum (ER) retention, indicating that these mutants are trafficking-defective, as reported in other disease-associated GPCRs. Notably, alkyl-OMPT, a potent synthetic agonist for LPA6 restored the defective cell surface expression of two of the ER-retained mutants, D63V and N246D, possibly by its chaperoning function that allows them to escape intracellular retention as well as proteasomal degradation. Furthermore, the alkyl-OMPT-rescued N246D mutant was shown be functional. Our findings encourage future application of pharmacoperone therapy for ARWH/HT patients with specific LPA6 mutations.

DOI PubMed

Lysophosphatidic acid-induced YAP/TAZ activation promotes developmental angiogenesis by repressing Notch ligand Dll4

Yasuda, D., Kobayashi, D., Akahoshi, N., Ohto-Nakanishi, T., Yoshioka, K., Takuwa, Y., Mizuno, S., Takahashi, S., and Ishii, S.

Journal of Clinical Investigation   129 ( 10 ) 4332 - 4349   2019年10月  [査読有り]

研究論文（学術雑誌）   国内共著

Lysophosphatidic acid (LPA) is a potent lipid mediator with various biological functions mediated through six G protein-coupled receptors (GPCRs), LPA1-6. Previous studies have demonstrated that LPA-Gα12/Gα13 signaling plays an important role in embryonic vascular development. However, the responsible LPA receptors and underlying mechanisms are poorly understood. Here, we show a critical role of LPA4 and LPA6 in developmental angiogenesis. In mice, Lpa4;Lpa6 double knockout (DKO) embryos were lethal due to global vascular deficiencies, and endothelial cell (EC)-specific Lpa4;Lpa6 DKO retinas had impaired sprouting angiogenesis. Mechanistically, LPA activated the transcriptional regulators YAP and TAZ through LPA4/LPA6-mediated Gα12/Gα13-Rho-ROCK signaling in ECs. YAP/TAZ knockdown increased β-catenin- and Notch intracellular domain (NICD)-mediated endothelial expression of the Notch ligand delta-like 4 (DLL4). Fibrin gel sprouting assay revealed that LPA4/LPA6, Gα12/Gα13, or YAP/TAZ knockdown consistently blocked EC sprouting, which was rescued by a Notch inhibitor. Of note, the inhibition of Notch signaling also ameliorated impaired retinal angiogenesis in EC-specific Lpa4;Lpa6 DKO mice. Overall, these results suggest that the Gα12/Gα13-coupled receptors LPA4 and LPA6 synergistically regulate endothelial Dll4 expression through YAP/TAZ activation. This could in part account for the mechanism of YAP/TAZ-mediated developmental angiogenesis. Our findings provide a novel insight into the biology of GPCR-activated YAP/TAZ.

DOI PubMed

Molecular mechanism of lysophosphatidic acid-induced hypertensive response

Kano K.

Scientific Reports ( Scientific Reports )  9 ( 1 )   2019年02月  [査読有り]

研究論文（学術雑誌）   国内共著

DOI

The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity

Yanagida K.

JCI insight ( JCI insight )  3 ( 24 ) e97293   2018年12月  [査読有り]

研究論文（学術雑誌）   国内共著

DOI PubMed

LPA5 signaling is involved in multiple sclerosis-mediated neuropathic pain in the cuprizone mouse model

Tsukahara R.

Journal of Pharmacological Sciences ( Journal of Pharmacological Sciences )  136 ( 2 ) 93 - 96   2018年02月  [査読有り]

研究論文（学術雑誌）   国内共著

Lysophosphatidic acid (LPA) and LPA1 receptor signaling play a crucial role in the initiation of peripheral nerve injury-induced neuropathic pain through the alternation of pain-related genes/proteins expression and demyelination. However, LPA and its signaling in the brain are still poorly understood. In the present study, we revealed that the LPA5 receptor expression in corpus callosum elevated after the initiation of demyelination, and the hyperalgesia through Aδ-fibers following cuprizone-induced demyelination was mediated by LPA5 signaling. These data suggest that LPA5 signaling may play a key role in the mechanisms underlying neuropathic pain following demyelination in the brain.

DOI PubMed

Identification of optineurin as an interleukin-1 receptor-associated kinase 1-binding protein and its role in regulation of MyD88-dependent signalling

Tanishima M.

Journal of Biological Chemistry ( Journal of Biological Chemistry )  292 ( 42 ) 17250 - 17257   2017年10月  [査読有り]

研究論文（学術雑誌）   国内共著

Upon stimulation of toll-like receptors with various microbial ligands, induction of a variety of inflammatory genes is elicited by activation of a myeloid differentiation primary-response protein 88 (MyD88)-dependent signaling pathway. Interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) plays an essential role in this pathway by activating nuclear factor kappa B (NF-kappa B) and mitogen-activated kinases (MAPKs). Here, we identified optineurin (OPTN) as an IRAK1-binding protein by yeast two-hybrid screening using IRAK1 as bait. A C-terminal fragment of OPTN harboring a ubiquitin-binding domain was co-immunoprecipitated with IRAK1. In reporter analyses, overexpression of OPTN inhibited IL-1 beta-, IRAK1-, and LPS-induced NF-kappa B activation. Consistently, OPTN deficiency resulted in increased NF-kappa B activation in response to IL-1 beta/LPS stimulation. To address the mechanisms underlying the inhibitory effect of OPTN on NF-kappa B signaling, we focused on tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), which is an adaptor protein of IRAK1 and upon polyubiquitination plays a crucial role during NF-kappa Bactivation. Overexpression of OPTN prevented TRAF6 polyubiquitination. Furthermore, OPTN H486R mutant, which is unable to recruit the deubiquitinase CYLD, failed to inhibit IRAK1-induced NF-kappa Bactivation. These results suggest that the IRAK1-binding protein OPTN negatively regulates IL-1 beta/LPS-induced NF-kappa Bactivation by preventing polyubiquitination of TRAF6.

DOI PubMed

Lysophosphatidic Acid Receptor 4 Activation Augments Drug Delivery in Tumors by Tightening Endothelial Cell-Cell Contact

Takara K.

Cell Reports ( Cell Reports )  20 ( 9 ) 2072 - 2086   2017年08月  [査読有り]

研究論文（学術雑誌）   国内共著

Vascular normalization in tumors may improve drug delivery and anti-tumor immunity. Angiogenesis inhibitors induce hypoxia, which may facilitate malignant progression; therefore, we investigated other methods to promote vascular maturation. Here, we show that lysophosphatidic acid (LPA) enhances blood flow by promoting fine vascular networks, thereby improving vascular permeability and suppressing tumor growth when combined with anti-cancer drug treatment. Six different G protein-coupled receptors have been identified as LPA receptors (LPA1-6). In studies using mutant mice, we found that LPA4 is involved in vascular network formation. LPA4 activation induces circumferential actin bundling beneath the cell membrane and enhances linear adherens junction formation by VE-cadherin in endothelial cells. Therefore, we conclude that activation of LPA4 is a promising approach for vascular regulation.

DOI PubMed

TDAG8 involved in initiating inflammatory hyperalgesia and establishing hyperalgesic priming in mice

Dai S.

Scientific Reports ( Scientific Reports )  7   41415   2017年02月  [査読有り]

研究論文（学術雑誌）   国際共著

Chronic pain, resulting from injury, arthritis, and cancer, is often accompanied by inflammation. High concentrations of protons found in inflamed tissues results in tissue acidosis, a major cause of pain and hyperalgesia. Acidosis signals may mediate a transition from acute to chronic hyperalgesia (hyperalgesic priming) via proton-sensing G-protein-coupled receptors (GPCRs). The expression of T-cell death-associated gene 8 (TDAG8), a proton-sensing GPCR, is increased during inflammatory hyperalgesia. Attenuating TDAG8 expression in the spinal cord inhibits bone cancer pain, but whether TDAG8 is involved in inflammatory hyperalgesia or hyperalgesic priming remains unclear. In this study, we used TDAG8-knockout or -knockdown to explore the role of TDAG8 in pain. Suppressed TDAG8 expression delayed the onset of inflammatory hyperalgesia and shortened hyperalgesic time in mice. In a dual acid-injection model (acid [pH 5.0] injected twice, 5 days apart), shRNA inhibition of TDAG8 shortened the duration of the second hyperalgesia. Similar results were found in TDAG8-deficient mice. The dual administration of TDAG8 agonist also confirmed that TDAG8 is involved in hyperalgsic priming. Accordingly, TDAG8 may mediate acidosis signals to initiate inflammatory hyperalgesia and establish hyperalgesic priming.

DOI PubMed

Involvement of TRPV1 and TDAG8 in Pruriception Associated with Noxious Acidosis

Lin S.H.

Journal of Investigative Dermatology ( Journal of Investigative Dermatology )  137 ( 1 ) 170 - 178   2017年01月  [査読有り]

研究論文（学術雑誌）   国際共著

Itch and pain are closely related but are distinct sensations. Intradermal injection of acid generates pain in both rodents and humans; however, few studies have addressed the intriguing question of whether acid (protons) can evoke itch like other algogens by spatial contrast activation of single nociceptors. Here, we report that (i) citric acid (0.2 mol/L) pH-dependently induced a scratching response in mice when applied intradermally to nape or cheek skin, (ii) acidified buffer elevated intracellular calcium levels in dorsal root ganglion pruriceptors, and (iii) injection of intradermal citric acid (pH 3.0) into the nape induced a pruritogen-like but not algogen-like c-Fos immunoreactivity pattern in the cervical spinal cord. Using pharmacological and genetic approaches, we identified potential acid-sensing channels/receptors involved in acidic citrate-evoked itch. Results indicate that TRPV1, but neither ASIC3 nor TRPA1, is involved in the acidic citrate-induced scratching response. Furthermore, one of the proton-sensing G-protein-coupled receptors, TDAG8, was highly (similar to 71%) expressed in Nppb(+) dorsal root ganglion pruriceptors. Itch induced by acidic citrate, but not alpha-methyl-5-hydroxytryptamine, chloroquine, compound 48/80, or bile acid, was markedly decreased in TDAG8(-/-) mice. In a heterologous expression system, TDAG8 potentiated the acid-induced calcium response by regulating TRPV1. Thus, protons could evoke pruriception by acting on TDAG8 to regulate TRPV1 activation with its mechanism of future therapeutic relevance.

DOI PubMed

LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis.

Sumida, H., Noguchi, K., Kihara, Y., Abe, M., Yanagida, K., Hamano, F., Sato, S., Tamaki, K., Morishita. Y., Kano, M.R., Iwata, C., Miyazono, K., Sakimura, K., Shimizu, T., and Ishii, S.

Blood   116   5060 - 5070   2010年04月

研究論文（学術雑誌）   単著

The leukotriene B(4) receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis.

Kihara, Y., Yokomizo, T., Kunita, A., Morishita, Y., Fukayama, M., Ishii, S., and Shimizu, T.

Biochem. Biophys. Res. Commun.   394   673 - 678   2010年01月

研究論文（学術雑誌）  

Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1.

Iwabu, M., Yamauchi, T., Okada-Iwabu, M., Sato, K., Nakagawa, T., Funata, M., Yamaguchi, M., Namiki, S., Nakayama, R., Tabata, M., Ogata, H., Kubota, N., Takamoto, I., Hayashi, Y.K., Yamauchi, N., Waki, H., Fukayama, M., Nishino, I., Tokuyama, K., Ueki, K., Oike, Y., Ishii, S., Hirose, K., Shimizu, T., Touhara, K., and Kadowaki, T.

Nature   464   1313 - 1319   2010年01月

研究論文（学術雑誌）  

Role of PAF receptor in proinflammatory cytokine expression in the dorsal root ganglion and tactile allodynia in a rodent model of neuropathic pain.

Hasegawa, S., Kohro, Y., Shiratori, M., Ishii, S., Shimizu, T., Tsuda, M., and Inoue, K.

PLoS One   5   e10467   2010年01月

研究論文（学術雑誌）  

The G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) facilitates tumor development by serving as an extracellular pH sensor. (Direct submission).

Ihara, Y., Kihara, Y., Hamano, F., Yanagida, K., Morishita, Y., Kunita, A., Yamori, T., Fukayama, M., Aburatani, H., Shimizu, T., and *Ishii, S.

Proc. Natl. Acad. Sci. U. S. A.   107   17309–17314   2010年01月

研究論文（学術雑誌）  

Opposing effects of platelet-activating factor and lyso-platelet activating factor on neutrophil and platelet activation.

Welch, E.J., Naikawadi, R.P., Li, Z., Lin, P., Ishii, S., Shimizu, T., Tiruppathi, C., Du, X., Subbaiah, P.V., and Ye, R.D.

Mol. Pharmacol.   75   227 - 234   2009年01月

研究論文（学術雑誌）  

Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of pro-inflammatory cytokine production in peritoneal macrophages.

Mogi, C., Tobo, M., Tomura, H., Murata, N., He, X.-d., Sato, K., Kimura, T., Ishizuka, T., Sasaki, T., Sato, T., Kihara, Y., Ishii, S., Harada, A., and Okajima, F.

J. Immunol.   182   3243–3251   2009年01月

研究論文（学術雑誌）  

Identification and characterization of a novel lysophosphatidic acid receptor, p2y5/LPA6.

Yanagida, K., Masago, K., Nakanishi, H., Kihara, Y., Hamano, F., Tajima, Y., Taguchi, R., Shimizu T., and *Ishii, S.

J. Biol. Chem.   284   17731 - 17741   2009年01月

研究論文（学術雑誌）  

Non-Edg family lysophosphatidic acid (LPA) receptors. (Invited Review)

Ishii, S., Noguchi, K., and Yanagida, K.

Prostaglandins Other Lipid Mediat   89   57 - 65   2009年01月

研究論文（学術雑誌）  

A distinctive role of the leukotriene B4 receptor BLT1 in osteoclastic activity during bone loss. (Direct submission)

Hikiji, H., *Ishii, S., Yokomizo, T., Takato, T., and Shimizu, T.

Proc. Natl. Acad. Sci. U. S. A.   106   21294 - 21299   2009年01月

研究論文（学術雑誌）  

Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis. (Direct submission)

Kihara, Y., Matsushita, T., Kita, Y., Uematsu, S., Akira, S., Kira, J.-i., Ishii, S., and Shimizu, T.

Proc. Natl. Acad. Sci. U. S. A.   106   21807 - 21812   2009年01月

研究論文（学術雑誌）  

The roles of prostanoids, leukotrienes, and platelet-activating factor in bone metabolism and disease. (Invited Review)

Hikiji H., Takato T., Shimizu T., and Ishii S.

Prog. Lipid Res.   47   107 - 126   2008年01月

研究論文（学術雑誌）  

Endothelial cysteinyl leukotriene 2 receptor (CysLT2R) expression mediates myocardial ischemia-reperfusion injury.

Jiang, W., Hall, S.R., Moos, M.P.W., Cao, R.Y., Ishii, S., Ogunyankin, K.O., Melo, L.G., and Funk, C.D.

Am. J. Pathol.   172   592 - 602   2008年01月

研究論文（学術雑誌）  

Platelet-activating factor production in the spinal cord of experimental allergic encephalomyelitis mice via the group IVA cytosolic PLA2-LysoPAFAT axis.

Kihara, Y., Yanagida, K., Masago, K., Kita, Y., Hishikawa, D., Shindou, H., Ishii, S., and Shimizu, T.

J. Immunol.   181   5008 - 5014   2008年01月

研究論文（学術雑誌）  

Cysteinyl leukotriene 2 receptor-mediated vascular permeability via transendothelial vesicle transport.

Moos, M.P.W., Mewburn, J.D., Kan, F.W.K., Ishii, S., Abe, M., Sakimura, K., Noguchi, K., Shimizu, T., and Funk, C.D.

FASEB J   22   4352 - 4362   2008年01月

研究論文（学術雑誌）  

Immunomodulation by n-3- vs. n-6-rich lipid emulsions in murine acute lung injury – role of platelet-activating factor receptor.

Schaefer, M.B., Ott, J., Mohr, A., Bi, M.H., Grosz, A., Weissmann, N., Ishii, S., Grimminger, F., Seeger, W., and Mayer, K.

Crit. Care Med.   35   544 - 554   2007年01月

研究論文（学術雑誌）  

LPA4/p2y9/GPR23 mediates Rho-dependent morphological changes in a rat neuronal cell line.

Yanagida, K., *Ishii, S., Hamano, F., Noguchi, K., and Shimizu, T.

J. Biol. Chem.   282   5814 - 5824   2007年01月

研究論文（学術雑誌）  

A single enzyme catalyzes both PAF production and membrane biogenesis of inflammatory cells: cloning and characterization of acetyl-CoA:lyso-PAF acetyltransferase.

Shindou, H., Hishikawa, D., Nakanishi, H., Harayama, T., Ishii, S., Taguchi, R., and Shimizu, T.

J. Biol. Chem.   282   6532 - 6539   2007年01月  [査読有り]

研究論文（学術雑誌）   単著

Role of platelet-activating factor in pneumolysin-induced acute lung injury.

Witzenrath, M., Gutbier, B., Owen, J.S., Schmeck, B., Mitchell, T.J., Mayer, K., Thomas, M.J., Ishii, S., Rosseau, S., Suttorp, N., and Schütte, H.

Crit. Care Med.   35   1756 - 1762   2007年01月

研究論文（学術雑誌）  

Reduced pain behaviors and ERK activation in primary sensory neurons by peripheral tissue injury in mice lacking platelet-activating factor receptor.

Tsuda, M., Ishii, S., Masuda, T., Hasegawa, S., Nakamura, K., Nagata, K., Yamashita, T., Furue, H., Tozaki-Saito, H., Yoshimura, M., Koizumi, S., Shimizu, T., and Inoue, K.

J. Neurochem.   102   1658 - 1668   2007年01月

研究論文（学術雑誌）  

Involvement of the platelet activating factor receptor in host defense against Streptococcus pneumoniae during postinfluenza pneumonia.

van der Sluijs, K.F., van Elden, L.J.R., Nijhuis, M., Schuurman, R., Florquin, S., Shimizu, T., Ishii, S., Jansen, H.M., Lutter, R., and van der Poll, T.

Am. J. Physiol.   290   L194 - L199   2006年01月

研究論文（学術雑誌）  

Attenuation of folic acid-induced renal inflammatory injury in platelet-activating factor receptor-deficient mice.

Doi, K., Okamoto, K., Negishi, K., Suzuki, Y., Nakao, A., Fujita, T., Toda, A., Yokomizo, T., Kita, Y., Kihara, Y., Ishii, S., Shimizu, T., and Noiri, E.

Am. J. Pathol.   168   1413 - 1424   2006年01月

研究論文（学術雑誌）  

Identification of T cell death-associated gene 8 (TDAG8) as a novel acid sensing G-protein-coupled receptor.

Ishii, S., Kihara, Y., and Shimizu, T.

J. Biol. Chem.   280   9083 - 9087   2005年01月

研究論文（学術雑誌）  

Stimulation of erythrocyte ceramide formation by platelet activating factor.

46. Lang, P.A., Kempe, D.S., Tanneur, V., Eisele, K., Klarl, B.A., Myssina, S., Jendrossek, V., Ishii, S., Shimizu, T., Waidmann, M., Hessler, G., Huber, S.M., Lang, F., and Wieder, T.

J. Cell Sci.   118   1233 - 1243   2005年01月

研究論文（学術雑誌）  

Priming effect of lipopolysaccharide on acetyl-CoA:lyso-PAF acetyltransferase is MyD88 and TRIF independent.

Shindou, H., Ishii, S., Yamamoto, M., Takeda, K., Akira, S., and Shimizu, T.

J. Immunol.   175   1177 - 1183   2005年01月

研究論文（学術雑誌）  

Staphylococcal lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating factor receptor.

Zhang, Q., Mousdicas, N., Yi, Q., Al-Hassani, M., Billings, S.D., Perkins, S.M., Howard, K.M., Ishii, S., Shimizu, T., and Travers, J.B.

J. Clin. Invest.   115   2855 - 2861   2005年01月

研究論文（学術雑誌）  

Dual phase regulation of experimental allergic encephalomyelitis by platelet-activating factor.

Kihara, Y., Ishii, S., Kita, Y., Toda, A., Shimada, A., and Shimizu, T.

J. Exp. Med.   202   853 - 863   2005年01月

研究論文（学術雑誌）  

Recruitment of katanin p60 by phosphorylated NDEL1, a LIS1 interacting protein, is essential for mitotic cell division and neuronal migration.

Toyo-oka, K., Sasaki, S., Yano, Y., Mori, D., Kobayashi, T., Toyoshima, Y.Y., Tokuoka, S.M., Ishii, S., Shimizu, T., Muramatsu, M., Hiraiwa, N., Yoshiki, A., Wynshaw-Boris, A., and Hirotsune, S.

Hum. Mol. Genet.   14   3113 - 3128   2005年01月

研究論文（学術雑誌）  

Platelet activating factor receptor deficient mice have an improved host defense against pneumococcal pneumonia.

Rijneveld, A.W., Weijer, S., Florquin, S., Speelman, P., Shimizu, T., Ishii, S., and van der Poll, T.

J. Infect. Dis.   189   711 - 716   2004年01月

研究論文（学術雑誌）  

Trophic signals acting via phosphatidylinositol-3 kinase are required for normal pre-implantation mouse embryo development.

Lu, D.P., Chandrakanthan, V., Cahana, A., Ishii, S., and O'Neill, C.

J. Cell Sci.   117   1567 - 1576   2004年01月

研究論文（学術雑誌）  

Platelet-activating factor receptor develops airway hyperresponsiveness independently of airway inflammation in a murine asthma model.

Ishii, S., Nagase, T., Shindou, H., Takizawa, H., Ouchi, Y., and Shimizu, T.

J. Immunol.   172   7095 - 7102   2004年01月

研究論文（学術雑誌）  

Absence of platelet-activating factor receptor protects mice from osteoporosis following ovariectomy.

Hikiji, H., *Ishii, S., Shindou, H., Takato, T., and Shimizu, T.

J. Clin. Invest.   114   85 - 93   2004年01月

研究論文（学術雑誌）  

Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization.

Angeli, V, Llodrá, J., Rong, J.X., Satoh, K, Ishii, S., Shimizu, T., Fisher, E.A., and Randolph, G.J.

Immunity   21   561 - 574   2004年01月

研究論文（学術雑誌）  

Platelet-activating factor receptor deficient mice show an unaltered clearance of Haemophilus influenzae from their respiratory tract.

Branger, J., Wieland, C.W., Florquin, S., Maris, N.A., Pater, J.M., Speelman, P., Shimizu, T., Ishii, S., and van der Poll, T.

Shock   22   543 - 547   2004年01月

研究論文（学術雑誌）  

Preparation of 7-substituted ginkgolide derivatives: potent platelet activating factor (PAF) receptor antagonists.

Vogensen, S.B., Strømgaard, K., Shindou, H., Jaracz, S., Suehiro, M., Ishii, S., Shimizu, T., and Nakanishi, K.

J. Med. Chem.   46   601 - 608   2003年01月

研究論文（学術雑誌）  

A potent inhibitor of cytosolic phospholipase A2, arachidonyl trifluoromethyl ketone, attenuates LPS-induced lung injury in mice.

Nagase, T., Uozumi, N., Aoki-Nagase, T., Terawaki, K., Ishii, S., Tomita, T., Yamamoto, H., Hashizume, K., Ouchi, Y., and Shimizu, T.

Am. J. Physiol.   284   L720 - L726   2003年01月

研究論文（学術雑誌）  

Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the Edg family.

Noguchi, K., Ishii, S., and Shimizu, T.

J. Biol. Chem.   278   25600 - 25606   2003年01月

研究論文（学術雑誌）  

Involvement of platelet-activating factor and LIS1 in neuronal migration.

Tokuoka, S.M., Ishii, S., Kawamura, N., Satoh, M., Shimada, A., Sasaki, S., Hirotsune, S., Wynshaw-Boris, A., and Shimizu, T.

Eur. J. Neurosci.   18   563 - 570   2003年01月

研究論文（学術雑誌）  

Experimental Trypanosoma cruzi infection in platelet-activating factor-deficient mice.

Talvani, A., Santana, G., Barcelos, L.S., Ishii, S., Shimizu, T., Romanha, Á.J., Silva, J.S., Soares, M.B.P., and Teixeira, M.M.

Microb. Infect.   5   789 - 796   2003年01月

研究論文（学術雑誌）  

Role of PAF receptors during intestinal ischemia and reperfusion injury. A comparative study between PAF receptor-deficient mice and PAF receptor antagonist treatment.

Souza, D.G., Pinho, V., Soares, A.C., Shimizu, T., Ishii, S., and Teixeira, M.M.

Br. J. Pharmacol.   139   733 - 740   2003年01月

研究論文（学術雑誌）  

Host response of platelet-activating factor receptor-deficient mice during pulmonary tuberculosis.

Weijer, S., Leemans, J.C., Florquin, S., Shimizu, T., Ishii, S., and van der Poll, T.

Immunology   109   552 - 556   2003年01月

研究論文（学術雑誌）  

Airway hyperresponsiveness in transgenic mice overexpressing platelet-activating factor receptor is mediated via an atropine sensitive pathway.

Nagase, T., Ishii, S., Shindou, H., Ouchi, Y., and Shimizu, T.

Am. J. Resp. Crit. Care Med.   165   200 - 205   2002年01月

研究論文（学術雑誌）  

Platelet-activating factor receptor. (Review)

Honda, Z., Ishii, S., and Shimizu, T.

J. Biochem.   131   773 - 779   2002年01月

研究論文（学術雑誌）  

Platelet-activating factor drives eotaxin production in an allergic pleurisy in mice.

Klein, A., Pinho, V., Alessandrini, A.L., Shimizu, T., Ishii, S., and Teixeira, M.M.

Br. J. Pharmacol.   135   1213 - 1218   2002年01月  [査読有り]

研究論文（学術雑誌）   単著

Receptor-dependent metabolism of platelet-activating factor in murine macrophages.

Ohshima, N., Ishii, S., Izumi, T., and Shimizu, T.

J. Biol. Chem.   277   9722 - 9727   2002年01月

研究論文（学術雑誌）  

A pivotal role of cytosolic phospholipase A2 in bleomycin-induced pulmonary fibrosis.

Nagase, T., Uozumi, N., Ishii, S., Kita, Y., Yamamoto, H., Ohga, E., Ouchi, Y., and Shimizu, T.

Nature Med.   8   480 - 484   2002年01月

研究論文（学術雑誌）  

Block of the background K+ channel, TASK-1, contributes to the arrhythmogenic effects of platelet-activating factor.

Barbuti, A., Ishii, S., Shimizu, T., Robinson, R.B., and Feinmark, S.J.

Am. J. Physiol.   282   H2024 - H2030   2002年01月

研究論文（学術雑誌）  

Characterization of mouse cysteinyl leukotriene receptors; mCysLT1 and mCysLT2. Differential pharmacological properties and tissue distribution.

Ogasawara, H., Ishii, S., Yokomizo, T., Kakinuma, T., Komine, M., Tamaki, K., Shimizu, T., and Izumi, T.

J. Biol. Chem.   277   18763 - 18768   2002年01月

研究論文（学術雑誌）  

Platelet-activating factor receptor. (Review)

Ishii, S., Nagase, T., and Shimizu, T.

Prostaglandins Other Lipid Mediat.   68-69   599 - 609   2002年01月

研究論文（学術雑誌）  

Ginkgolide derivatives for photolabeling studies: preparation and pharmacological evaluation.

Strømgaard, K., Saito, D.R., Shindou, H., Ishii, S., Shimizu, T., and Nakanishi, K.

J. Med. Chem.   45   4038 - 4046   2002年01月

研究論文（学術雑誌）  

Role of the platelet-activating factor (PAF) receptor during pulmonary infection with gram negative bacteria.

Soares, A.C., Pinho, V.S., Souza, D.G., Shimizu, T., Ishii, S., Nicoli, J.R., and Teixeira, M.M.

Br. J. Pharmacol.   137   621 - 628   2002年01月

研究論文（学術雑誌）  

Evidence for the autocrine induction of capacitation of mammalian spermatozoa.

Wu, C., Stojanov, T., Chami, O., Ishii, S., Shimizu, T., Li, A., and O'Neill, C.

J. Biol. Chem.   276   26962 - 26968   2001年01月

研究論文（学術雑誌）  

Single nucleotide polymorphism of human platelet-activating factor receptor impairs G-protein activation.

Fukunaga, K., Ishii, S., Asano, K., Yokomizo, T., Shiomi, T., Shimizu, T., and Yamaguchi, K.

J. Biol. Chem.   276   43025 - 43030   2001年01月

研究論文（学術雑誌）  

Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice. (Invited Review)

Ishii, S. and Shimizu, T.

Prog. Lipid Res.   39   41 - 82   2000年01月

研究論文（学術雑誌）  

Interaction between neurone and glia mediated by platelet-activating factor.

Aihara, M., Ishii, S., Kume, K. and Shimizu, T.

Genes Cells   5   397 - 406   2000年01月

研究論文（学術雑誌）  

Roles of cytosolic phospholipase A2 and platelet-activating factor receptor in the Ca-induced biosynthesis of PAF.

Shindou, H., Ishii, S., Uozumi, N. and Shimizu, T.

Biochem. Biophys. Res. Commun.   271   812 - 817   2000年01月

研究論文（学術雑誌）  

Acute lung injury by sepsis and acid aspiration: a key role of cytosolic phospholipase A2.

Nagase, T., Uozumi, N., Ishii, S., Kume, K., Izumi, T., Ouchi, Y. and Shimizu, T.

Nature Immunol.   1   42 - 46   2000年01月

研究論文（学術雑誌）  

Platelet-activating factor is not required for long-term potentiation in the hippocampal CA1 region.

Kobayashi, K., Ishii, S., Kume, K., Takahashi, T., Shimizu, T. and Manabe, T.

Eur. J. Neurosci.   11   1313 - 1316   1999年01月

研究論文（学術雑誌）  

Accelerated proliferation of the epidermal keratinocytes by the transgenic expression of the platelet-activating factor receptor.

Sato, S., Kume, K., Ito, C., Ishii, S. and Shimizu, T.

Arch. Dermatol. Res.   291   614 - 621   1999年01月

研究論文（学術雑誌）  

Platelet-activating factor mediates acid-induced lung injury in genetically engineered mice.

Nagase, T., Ishii, S., Kume, K., Uozumi, N., Izumi, T., Ouchi, Y. and Shimizu, T.

J. Clin. Invest.   104   1071 - 1076   1999年01月

研究論文（学術雑誌）  

Impaired anaphylactic responses with intact sensitivity to endotoxin in mice lacking a platelet-activating factor receptor.

Ishii, S., Kuwaki, T. et al

J. Exp. Med.   187   1779 - 1788   1998年01月

研究論文（学術雑誌）  

Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor.

Ishii, S., Nagase, T., Tashiro, F., Ikuta, K., Sato, S., Waga, I., Kume, K., Miyazaki, J. and Shimizu, T.

EMBO J.   16   133 - 142   1997年01月

研究論文（学術雑誌）  

Airway responsiveness in transgenic mice overexpressing platelet-activating factor receptor: roles of thromboxanes and leukotrienes.

Nagase, T., Ishii, S., Katayama, H., Fukuchi, Y., Ouchi, Y. and Shimizu, T.

Am. J. Resp. Crit. Care Med.   156   1621 - 1627   1997年01月

研究論文（学術雑誌）  

Lipid mediators modulate NMDA receptor currents in a Xenopus oocyte expression system.

Tabuchi, S., Kume, K., Aihara, M., Ishii, S., Mishina, M. and Shimizu, T.

Neurosci. Lett.   237   13 - 16   1997年01月

研究論文（学術雑誌）  

Role of cytosolic phospholipase A2 in allergic response and parturition.

Uozumi, N., Kume, K., Nagase, T., Nakatani, N., Ishii, S., Tashiro, F., Komagata, Y., Maki, K., Ikuta, K., Ouchi, Y., Miyazaki, J. and Shimizu, T.

Nature   390   618 - 622   1997年01月

研究論文（学術雑誌）  

A murine platelet-activating factor receptor gene: cloning, chromosomal localization and up-regulation of expression by lipopolysaccharide in peritoneal resident macrophages.

Ishii, S., Matsuda, Y., Nakamura, M., Waga, I., Kume, K., Izumi, T. and Shimizu, T.

Biochem. J.   314   671 - 678   1996年01月

研究論文（学術雑誌）  

Platelet-activating factor (PAF) positively auto-regulates the expression of human PAF receptor transcript 1 (leukocyte-type) through NF-κB. Biochem.

Mutoh, H., Ishii, S., Izumi, T., Kato, S. and Shimizu, T.

Biophys. Res. Commun.   205   1137 - 1142   1994年01月

研究論文（学術雑誌）  

A pSC101-par sequence-mediated study on the intracellular state of supercoiling of the pBR322 genome in Escherichia coli DNA topoisomerase I deletion mutant.

Ishii, S., Murakami, T. and Shishido, K.

FEMS Microbiol. Lett.   93   115 - 120   1992年01月

研究論文（学術雑誌）  

Synthesis of the N-terminal half of the tetracycline resistance protein of pBR322 is responsible for a high level of plasmid DNA supercoiling in Escherichia coli.

Murakami, T., Ishii, S. and Shishido, K.

J. Gen. Appl. Microbiol.   38   379 - 383   1992年01月

研究論文（学術雑誌）  

Mutagenesis studies on the amino acid residues involved in the iron-binding and the activity of human 5-lipoxygenase.

Ishii, S., Noguchi, M., Miyano, M., Matsumoto, T. and Noma, M.

Biochem. Biophys. Res. Commun.   182   1482 - 1490   1992年01月

研究論文（学術雑誌）  

Gyrase inhibitors increase the content of knotted DNA species of plasmid pBR322 in Escherichia coli.

Ishii, S., Murakami, T. and Shishido, K.

J. Bacteriol.   173   5551 - 5553   1991年01月

研究論文（学術雑誌）  

The presence of the region on pBR322 that encodes resistance to tetracycline is responsible for high levels of plasmid DNA knotting in Escherichia coli DNA topoisomerase I deletion mutant.

Shishido, K., Ishii, S. and Komiyama, N.

Nucleic Acids Res.   17   9749 - 9759   1989年01月

研究論文（学術雑誌）