{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:50:13Z","timestamp":1793379013829,"version":"4.5.0"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"abstract":"<jats:p>Introduction: TNF\u03b1-inducible matrix metalloproteinases (MMP) play a critical role in the process of airway remodelling in respiratory inflammatory disease including asthma. The cationic host defence peptide (CHDP) LL-37 is elevated in the lungs during airway inflammation. However, the impact of LL-37 on TNF\u03b1-driven processes is not well understood. Here, we examined the effect of LL-37 on TNF\u03b1-mediated responses in human bronchial epithelial cells (HBEC). \nMethods: We used a Slow Off-rate Modified Aptamer-based proteomics approach to define the HBEC proteome altered in response to TNF\u03b1. Abundance of selected protein candidates and signaling intermediates were examined using immunoassays, ELISA and Western blots, and mRNA abundance was examined by qRT-PCR.  \nResults: Proteomics analysis revealed that 124 proteins were significantly altered, 12 proteins were enhanced by \u22652-fold compared to unstimulated cells, in response to TNF\u03b1. MMP9 was the topmost increased protein in response to TNF\u03b1, enhanced by ~10-fold and MMP13 was increased by ~3-fold, compared to unstimulated cells. Furthermore, we demonstrated that LL-37 significantly suppressed TNF\u03b1-mediated MMP9 and MMP13 in HBEC. Mechanistic data revealed that TNF\u03b1-mediated MMP9 and MMP13 production is controlled by SRC kinase, and that LL-37 enhances related upstream negative regulators namely phosphoAKT(T308) and TNF\u03b1-mediated TNFAIP3 or A20. \nConclusions: The findings of this study suggest that LL-37 may play a role in intervening in the process of airway remodeling in chronic inflammatory respiratory disease such as asthma.  <\/jats:p>","DOI":"10.1159\/000537775","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T22:00:32Z","timestamp":1710280832000},"source":"Crossref","is-referenced-by-count":6,"title":["Human host defence peptide LL-37 suppresses TNF\u03b1-mediated matrix metalloproteinases MMP9 and MMP13, in human bronchial epithelial cells"],"prefix":"10.1159","author":[{"given":"Anthony","family":"Altieri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney Lynn","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padmanie","family":"Ramotar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahadevappa","family":"Hemshekhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Spicer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"van der Does","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeloffer","family":"Mookherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2024,3,12]]},"container-title":["Journal of Innate Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/jin\/article-pdf\/doi\/10.1159\/000537775\/4178362\/000537775.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/jin\/article-pdf\/doi\/10.1159\/000537775\/4178362\/000537775.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:06:29Z","timestamp":1745420789000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000537775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,12]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/000537775","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.25374955","asserted-by":"subject"}]},"ISSN":["1662-811X","1662-8128"],"issn-type":[{"value":"1662-811X","type":"print"},{"value":"1662-8128","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,12]]}}}