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• W3178733483 abstract "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.To investigate the molecular mechanisms underlying carvedilol efficacy in rosacea treatment.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-α, and IL-1β) evaluation. An in vivo 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.Rosacea skin lesions exhibited more pronounced inflammatory cell infiltration than peripheral areas, with profound macrophage infiltration and inflammatory cytokines (TLR2, kallikrein 5, cathelicidin, TNF-α, and IL-1β). In vivo, carvedilol alleviated inflammation in LL-37 mice, down-regulating TLR2, KLK5, and cathelicidin expression. In vitro, 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.Carvedilol is effective against rosacea, with inhibition of macrophage TLR2 expression as a novel anti-inflammatory mechanism." @default.
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• W3178733483 date "2021-07-12" @default.
• W3178733483 modified "2023-10-14" @default.
• W3178733483 title "A Novel Mechanism of Carvedilol Efficacy for Rosacea Treatment: Toll-Like Receptor 2 Inhibition in Macrophages" @default.
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• W3178733483 doi "https://doi.org/10.3389/fimmu.2021.609615" @default.
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