{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:11:28Z","timestamp":1792872688360,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kuwait Foundation for the Advancement of Sciences","award":["RA AH 2023-023"],"award-info":[{"award-number":["RA AH 2023-023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Matrix metalloproteinase-9 (MMP-9) and lipopolysaccharide (LPS) levels are known to be elevated in obesity and contribute to metabolic dysfunction. 2-(1\u2032H-indole-3\u2032-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous ligand of the aryl hydrocarbon receptor (AhR), has been implicated in the regulation of inflammatory responses. This study aimed to determine whether ITE can inhibit LPS-induced MMP-9 expression in monocytic cells and to explore the underlying signaling mechanisms involved. Human monocytic THP-1 cells and primary human monocytes were treated with LPS in the presence or absence of ITE. MMP-9 mRNA and protein levels were assessed using quantitative real-time PCR and ELISA, respectively, while gelatin zymography was employed to evaluate MMP-9 enzymatic activity. Chromatin immunoprecipitation followed by qPCR (ChIP-qPCR) was performed to assess NF-\u03baB and AP-1 binding to the MMP-9 promoter region. Our findings demonstrate that ITE significantly suppresses LPS-induced MMP-9 gene and protein expression. This suppression is associated with a marked reduction in LPS-induced NF-\u03baB and AP-1 transcriptional activity. ChIP-qPCR confirmed that ITE attenuates the recruitment of NF-\u03baB and AP-1 to the MMP-9 promoter, thereby inhibiting its transcription. In summary, ITE downregulates LPS-induced MMP-9 expression by interfering with NF-\u03baB\/AP-1 signaling, suggesting a potential anti-inflammatory mechanism that could be relevant in the context of MMP-9-driven inflammatory conditions.<\/jats:p>","DOI":"10.3390\/ijms26125663","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T03:53:12Z","timestamp":1749786792000},"page":"5663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tryptophan Metabolite ITE Attenuates LPS-Induced MMP-9 via NF-\u03baB\/AP-1 in Monocytes"],"prefix":"10.3390","volume":"26","author":[{"given":"Fatemah","family":"Bahman","sequence":"first","affiliation":[{"name":"Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem","family":"Akhter","sequence":"additional","affiliation":[{"name":"Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2061-5895","authenticated-orcid":false,"given":"Shihab","family":"Kochumon","sequence":"additional","affiliation":[{"name":"Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5409-3829","authenticated-orcid":false,"given":"Fahd","family":"Al-Mulla","sequence":"additional","affiliation":[{"name":"Translational Research Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5746-0743","authenticated-orcid":false,"given":"Rasheed","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E740","DOI":"10.1152\/ajpendo.00302.2006","article-title":"Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes","volume":"292","author":"Creely","year":"2007","journal-title":"Am. 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