{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:17:34Z","timestamp":1785799054162,"version":"3.56.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:00:00Z","timestamp":1626048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Rosacea, a chronic inflammatory skin disorder etiologically associated with immune cells and the antibacterial peptide cathelicidin LL-37, can be effectively treated by oral carvedilol administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the molecular mechanisms underlying carvedilol efficacy in rosacea treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Skin samples of patients with rosacea were subjected to histopathological (hematoxylin and eosin) and immunohistochemical (CD68, Toll-like receptor 2 (TLR2), kallikrein 5, cathelicidin, TNF-\u03b1, and IL-1\u03b2) evaluation. An <jats:italic>in vivo<\/jats:italic> murine rosacea-like inflammation model was established by LL-37 intradermal injection with or without carvedilol gavage-based pretreatment. Erythema proportion (Image J) and skin redness (L*a*b colorimetry) were quantified. Murine skin samples underwent pathological examination for inflammatory status and immunofluorescence staining. Murine skin and lipopolysaccharide-stimulated RAW 264.7 cells with or without carvedilol pretreatment were evaluated by quantitative reverse transcription-polymerase chain reaction and western blotting. Clinical facial images of patients were obtained using the VISIA skin analysis system before, 4, and 6 months following oral carvedilol administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rosacea skin lesions exhibited more pronounced inflammatory cell infiltration than peripheral areas, with profound macrophage infiltration and inflammatory cytokines (TLR2, kallikrein 5, cathelicidin, TNF-\u03b1, and IL-1\u03b2). <jats:italic>In vivo<\/jats:italic>, carvedilol alleviated inflammation in LL-37 mice, down-regulating TLR2, KLK5, and cathelicidin expression. <jats:italic>In vitro<\/jats:italic>, carvedilol decreased TLR2 expression in RAW 264.7 cells, further reducing KLK5 secretion and LL-37 expression and ultimately inhibiting rosacea-like inflammatory reactions. Clinical manifestations and facial redness obviously improved during 6-month follow-up with systemic carvedilol administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Carvedilol is effective against rosacea, with inhibition of macrophage TLR2 expression as a novel anti-inflammatory mechanism.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.609615","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T08:49:20Z","timestamp":1626079760000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["A Novel Mechanism of Carvedilol Efficacy for Rosacea Treatment: Toll-Like Receptor 2 Inhibition in Macrophages"],"prefix":"10.3389","volume":"12","author":[{"given":"Jiawen","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2017.08.037","article-title":"Standard Classification and Pathophysiology of Rosacea: The 2017 Update by the National Rosacea Society Expert Committee","volume":"78","author":"Gallo","year":"2018","journal-title":"J Am Acad Dermatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16481","article-title":"Incidence and Prevalence of Rosacea: A Systematic Review and Meta-Analysis","volume":"179","author":"Gether","year":"2018","journal-title":"Br J Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2017.08.037","article-title":"Dermatology, Standard Classification and Pathophysiology of Rosacea: The 2017 Update by the National Rosacea Society Expert Committee","volume":"78","author":"Gallo","year":"2018","journal-title":"J Am Acad Dermatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13143","article-title":"Integrative Concepts of Rosacea Pathophysiology, Clinical Presentation and New Therapeutics","volume":"26","author":"Holmes","year":"2017","journal-title":"Exp Dermatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nm1616","article-title":"Increased Serine Protease Activity and Cathelicidin Promotes Skin Inflammation in Rosacea","volume":"13","author":"Yamasaki","year":"2007","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.351","article-title":"TLR2 Expression Is Increased in Rosacea and Stimulates Enhanced Serine Protease Production by Keratinocytes","volume":"131","author":"Yamasaki","year":"2011","journal-title":"J.o.i. 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