{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:03:55Z","timestamp":1791911035709,"version":"4.3.4"},"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>Rose Bengal Photodynamic Therapy (RB-PDT) offers dual therapeutic benefits by enhancing corneal stiffness and providing antibacterial activity, presenting significant potential for patients with keratoconus complicated by keratitis. Our purpose was to assess the effect of rose bengal photodynamic therapy (RB-PDT) on the expression of pro-inflammatory cytokines and chemokines, as well as on extracellular matrix (ECM)-related molecules, in lipopolysaccharide (LPS)-induced inflammation of keratoconus human corneal fibroblasts (KC-HCFs). Additionally, the involvement of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-\u03baB) signaling pathways which are downstream of the Toll-like receptor 4 (TLR4) pathway were examined.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>KC-HCFs were stimulated with varying concentrations of LPS (0\u201310 \u03bcg\/ml), which was followed by RB-PDT. The expression levels of interleukin-1\u03b2 (IL-1\u03b2), IL-6, IL-8, interferon alpha 2 (IFNA2), IFNB1, intercellular adhesion molecule 1 (ICAM-1), chemokine (C-C motif) ligand 4 (CCL-4), collagen I, collagen V, lysyl oxidase (LOX), transforming growth factor \u03b2 1(TGF-\u03b21) were measured using qPCR, ELISA, or western blot. The activation of the NF-\u03baB and MAPK pathways was assessed using qPCR and western blot.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>In LPS-induced inflammation of KC-HCFs, the expression of IL-6 was further amplified by the treatment with RB-PDT (p = 0.001). However, the activation of the MAPK and NF-\u03baB pathways did not increase following RB-PDT. Additionally, RB-PDT reduced the transcription of collagen I and collagen V (p\u22640.03), while the transcription of LOX and TGF-\u03b21 secretion remained unchanged in KC-HCFs exposed to LPS.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In LPS-induced inflammation of KC-HCFs treated with RB-PDT, despite the increased expression of pro-inflammatory cytokines, the activation of the TLR4 signaling pathways is lacking. RB-PDT may have no adverse effects on corneal scar formation of keratoconus corneas in the short term.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0318132","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T18:31:55Z","timestamp":1738002715000},"page":"e0318132","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["The cellular response of lipopolysaccharide-induced inflammation in keratoconus human corneal fibroblasts to RB-PDT: Insights into cytokines, chemokines and related signaling pathways"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9689-8887","authenticated-orcid":true,"given":"Ning","family":"Chai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Stachon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"H\u00e4cker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Amini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta","family":"Suiwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9701-8204","authenticated-orcid":true,"given":"Berthold","family":"Seitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Langenbucher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00f3ra","family":"Szentm\u00e1ry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"pone.0318132.ref001","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1097\/APO.0000000000000332","article-title":"Biochemical markers and alterations in keratoconus.","volume":"9","author":"Shetty R","year":"2020","journal-title":"Asia-Pacific J Ophthalmol."},{"key":"pone.0318132.ref002","doi-asserted-by":"crossref","first-page":"5372","DOI":"10.1167\/iovs.16-19677","article-title":"Differential molecular expression of extracellular matrix and inflammatory genes at the corneal cone apex drives focal weakening in keratoconus","volume":"57","author":"N Pahuja","year":"2016","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"pone.0318132.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-99805-9","article-title":"Keratoconus patients exhibit a distinct ocular surface immune cell and inflammatory profile","volume":"11","author":"S D\u2019Souza","year":"2021","journal-title":"Sci Rep"},{"key":"pone.0318132.ref004","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/eye.2015.63","article-title":"Keratoconus: An inflammatory disorder?","volume":"29","author":"V Galvis","year":"2015","journal-title":"Eye"},{"key":"pone.0318132.ref005","doi-asserted-by":"crossref","first-page":"108229","DOI":"10.1016\/j.exer.2020.108229","article-title":"Corneal fibroblasts: Function and markers","volume":"200","author":"K. 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