{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:19:00Z","timestamp":1792804740572,"version":"4.5.0"},"reference-count":60,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Otago Vice-Chancellor\u2019s Strategic Development Fund","award":["22H05577"],"award-info":[{"award-number":["22H05577"]}],"id":[{"id":"https:\/\/ror.org\/01jmxt844","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Maurice and Phyllis Paykel Trust grant","award":["22H05577"],"award-info":[{"award-number":["22H05577"]}],"id":[{"id":"https:\/\/ror.org\/05tx9pa51","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H05577"],"award-info":[{"award-number":["22H05577"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hydrogen sulfide (H2S), synthesized by cystathionine gamma-lyase (Cth), contributes to the inflammatory response observed in sepsis. This study examines the effect of Cth-derived H2S in adhesion molecules on endothelial cells of vital organs in mice in a cecal ligation puncture (CLP)-induced model of sepsis, using two different and complementary approaches: Cth gene deletion and pharmacological inhibition. Our findings revealed a decreased level of H2S-synthesizing activity (via Cth) in both Cth\u2212\/\u2212 mice and PAG-treated wild-type (WT) mice following CLP-induced sepsis. Both treatment groups had reduced MPO activity and expression of chemokines (MCP-1 and MIP-2\u03b1), adhesion molecules (ICAM-1 and VCAM-1), ERK1\/2 phosphorylation, and NF-\u03baB in the liver and lung compared with in CLP-WT mice. Additionally, we found that PAG treatment in Cth\u2212\/\u2212 mice had no additional effect on the expression of ERK1\/2 phosphorylation, NF-\u03baB, or the production of chemokines and adhesion molecules in the liver and lung compared to Cth\u2212\/\u2212 mice following CLP-induced sepsis. The WT group with sepsis had an increased immunoreactivity of adhesion molecules on endothelial cells in the liver and lung than the WT sham-operated control. The Cth\u2212\/\u2212, PAG-treated WT, and Cth\u2212\/\u2212 groups of mice showed decreased immunoreactivity of adhesion molecules on endothelial cells in the liver and lung following sepsis. Inhibition of H2S production via both approaches reduced adhesion molecule expression on endothelial cells and reduced liver and lung injury in mice with sepsis. In conclusion, this study demonstrates that H2S has an important role in the pathogenesis of sepsis and validates PAG use as a suited tool for investigating the Cth\/H2S-signalling axis in sepsis.<\/jats:p>","DOI":"10.3390\/ijms241713650","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:14:11Z","timestamp":1693822451000},"page":"13650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacological Inhibition and Genetic Deletion of Cystathionine Gamma-Lyase in Mice Protects against Organ Injury in Sepsis: A Key Role of Adhesion Molecules on Endothelial Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5593-7357","authenticated-orcid":false,"given":"Sumeet","family":"Manandhar","sequence":"first","affiliation":[{"name":"Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Chambers","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5367-205X","authenticated-orcid":false,"given":"Isao","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhav","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E2","DOI":"10.1503\/cmaj.160798","article-title":"Reducing the global burden of sepsis","volume":"189","author":"Dugani","year":"2017","journal-title":"CMAJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1056\/NEJMoa022139","article-title":"The epidemiology of sepsis in the United States from 1979 through 2000","volume":"348","author":"Martin","year":"2003","journal-title":"N. 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