Details of a Researcher

ZHANG Tianli

写真a

Affiliation

Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases

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Research Interests 【 display / non-display 】

Inflammatory responses
Sulfur biology
Micribiology
Immunology
Host defense

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Graduating School 【 display / non-display 】

　

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2011.07

Jiujiang University Faculty of Medicine Graduated
2015.04

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2019.03

Kumamoto University Graduate School of Medical Sciences Department of Microbiology Graduated
2013.04

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2015.03

Kumamoto University Graduate School of Medical Sciences Department of Immunology Graduated

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Graduate School 【 display / non-display 】

2015.04

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2019.03

Kumamoto University Graduate School, Division of Medicine Doctor's Course Completed
2013.04

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2015.03

Kumamoto University Graduate School, Division of Medicine Master's Course Completed

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Campus Career 【 display / non-display 】

2024.06

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Now

Akita University Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases Assistant Professor

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External Career 【 display / non-display 】

2024.06

　

　

Akita University Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases Assistant Professor
2022.10

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2024.05

Kumamoto University Faculty of Life Sciences
2020.10

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2022.09

Japan Society for the Promotion of Science
2019.04

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2020.09

Kumamoto University Faculty of Life Sciences

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Research Areas 【 display / non-display 】

Life Science / Medical biochemistry
Life Science / Immunology
Life Science / Immunology
Life Science / Medical biochemistry
Life Science / Bacteriology

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Research Achievements 【 display / non-display 】

◆Original paper【 display / non-display 】

Supersulfides suppress type-Ⅰ and type-Ⅱ interferon responses by blocking JAK/STAT signaling in macrophages.

Xiaoyan Li, Touya Toyomoto, Tianli Zhang, Chunyu Guo, Stephen Lindahl, Hiroyasu Tsutsuki, Ming Xian, Tomohiro Sawa

International immunology 2024.06

Research paper (journal)

Interferons (IFNs) are cytokines produced and secreted by immune cells when viruses, tumor cells, and so forth, invade the body. Their biological effects are diverse, including antiviral, cell growth-inhibiting, and antitumor effects. The main subclasses of interferons include type-I (e.g., IFN-α and IFN-β) and type-II (IFN-γ), which activate intracellular signals by binding to type-I and type-II IFN receptors, respectively. We have previously shown that when macrophages are treated with supersulfide donors, which have polysulfide structures in which three or more sulfur atoms are linked within the molecules, IFN-β-induced cellular responses, including signal transducer and activator of transcription 1 (STAT1) phosphorylation and inducible nitric oxide synthase (iNOS) expression, were strongly suppressed. However, the subfamily specificity of the suppression of IFN signals by supersulfides and the mechanism of this suppression are unknown. This study demonstrated that supersulfide donor N-acetyl-L-cysteine tetrasulfide (NAC-S2) can inhibit IFN signaling in macrophages stimulated not only with IFN-α/β but also with IFN-γ. Our data suggest that NAC-S2 blocks phosphorylation of Janus kinases (JAKs), thereby contributes to the inhibition of phosphorylation of STAT1. Under the current experimental conditions, hydrogen sulfide (H2S) donor NaHS failed to inhibit IFN signaling. Similar to NAC-S2, carbohydrate-based supersulfide donor thioglucose tetrasulfide (TGS4) was capable of strongly inhibiting tumor necrosis factor-αproduction, iNOS expression, and nitric oxide production from macrophages stimulated with lipopolysaccharide. Further understanding of molecular mechanisms how supersulfide donors exhibit their inhibitory actions towards JAK/STAT signaling is necessary basis for development of supersulfide-based therapeutic strategy against autoimmune disorders with dysregulated IFN signaling.

DOI PubMed

Regulation of innate immune and inflammatory responses by supersulfides.

Hiroyasu Tsutsuki, Tianli Zhang, Takaaki Akaike, Tomohiro Sawa

International immunology 2024.01 [Refereed]

Research paper (journal)

Innate immunity plays an important role in host defense against microbial infections. It also participates in activation of acquired immunity through cytokine production and antigen presentation. Pattern recognition receptors such as Toll-like receptors and nucleotide oligomerization domain-like receptors sense invading pathogens and associated tissue injury, after which inflammatory mediators such as pro-inflammatory cytokines and nitric oxide are induced. Supersulfides are molecular species possessing catenated sulfur atoms such as persulfide and polysulfide moieties. They have recently been recognized as important regulators in cellular redox homeostasis by acting as potent antioxidants and nucleophiles. In addition, recent studies suggested that supersulfides are critically involved in the regulation of innate immune and inflammatory responses. In this review, we summarize current knowledge of the chemistry and biology of supersulfides, with particular attention to their roles in regulation of innate immune and inflammatory responses. Studies with animal models of infection and inflammation demonstrated the potent anti-inflammatory functions of supersulfides such as blocking pro-inflammatory signaling cascades, reducing oxidative stresses, and inhibiting replication of microbial pathogens including severe acute respiratory syndrome coronavirus 2. Precise understanding of how supersulfides regulate innate immune responses is the necessary requirement for developing supersulfide-based diagnostic as well as therapeutic strategies against inflammatory disorders.

DOI PubMed

Thioglucose-derived tetrasulfide, a unique polysulfide model compound.

Stephen Lindahl, Meg Shieh, Tianli Zhang, Chunyu Guo, Jerome R Robinson, Tomohiro Sawa, Ming Xian

Redox biology 70 103045 - 103045 2024.01 [Refereed]

Research paper (journal)

Polysulfides have received increased interest in redox biology due to their role as the precursors of H2S and persulfides. However, the compounds that are suitable for biological investigations are limited to cysteine- and glutathione-derived polysulfides. In this work, we report the preparation and evaluation of a novel polysulfide derived from thioglucose, which represents the first carbohydrate-based polysulfide. This compound, thioglucose tetrasulfide (TGS4), showed excellent stability and water solubility. H2S and persulfide production from TGS4, as well as its associated antioxidative property were also demonstrated. Additionally, TGS4 was demonstrated to significantly induce cellular sulfane sulfur level increase, in particular for the formation of hydropersulfides/trisulfides. These results suggest that TGS4 is a useful tool for polysulfide research.

DOI PubMed

Redox Biology Involved in the Toxicity of Enterohemorrhagic <i>Escherichia coli</i> Toxin SubAB

Tsutsuki Hiroyasu, Zhang Tianli, Sawa Tomohiro

YAKUGAKU ZASSHI ( The Pharmaceutical Society of Japan ) 144 ( 1 ) 57 - 60 2024.01

Research paper (journal)

DOI PubMed CiNii Research

Redox Regulation of Xenobiotics by Reactive Sulfur and Supersulfide Species.

Tianli Zhang, Takaaki Akaike, Tomohiro Sawa

Antioxidants & redox signaling 2023.09 [Refereed]

Research paper (journal)

Significance: Routine exposure to xenobiotics is unavoidable during our lifetimes. Certain xenobiotics are hazardous to human health, and are metabolized in the body to render them less toxic. During this process, several detoxification enzymes cooperatively metabolize xenobiotics. Glutathione (GSH) conjugation plays an important role in the metabolism of electrophilic xenobiotics. Recent Advances: Recent advances in reactive sulfur and supersulfide (RSS) analyses showed that persulfides and polysulfides bound to low-molecular-weight thiols, such as GSH, and to protein thiols are abundant in both eukaryotes and prokaryotes. The highly nucleophilic nature of hydropersulfides and hydropolysulfides contributes to cell protection against oxidative stress and electrophilic stress. Critical Issues: In contrast to GSH conjugation to electrophiles that is aided by glutathione S-transferase (GST), persulfides and polysulfides can directly form conjugates with electrophiles without the catalytic actions of GST. The polysulfur bonds in the conjugates are further reduced by perthioanions and polythioanions derived from RSS to form sulfhydrated metabolites that are no longer electrophilic but rather nucleophilic, and differ from metabolites that are formed via GSH conjugation. Future Directions: In view of the abundance of RSS in cells and tissues, metabolism of xenobiotics that is mediated by RSS warrants additional investigations, such as studies of the impact of microbiota-derived RSS on xenobiotic metabolism. Metabolites formed from reactions between electrophiles and RSS may be potential biomarkers for monitoring exposure to electrophiles and for studying their metabolism by RSS.

DOI PubMed

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