Tranilast alleviates skin inflammation and fibrosis in rosacea-like mice induced by long-term exposure to LL-37.

Rosacea, a prevalent chronic facial inflammatory condition, afflicts millions worldwide. Its multifaceted pathogenesis poses challenges for effective treatment. Tranilast (TR), an analog of a tryptophan metabolite, has demonstrated anti-inflammatory and anti-fibrotic properties across various diseases. Yet, its potential in rosacea treatment remains understudied. Here, we induced rosacea-like symptoms in mice via prolonged LL-37 injections and administered TR intervention. Our findings reveal that TR mitigated skin lesions, reduced skin thickness, and suppressed inflammatory cell infiltration within the dermis of LL-37 mice. Notably, TR downregulated the expression of rosacea-associated inflammatory cytokines (TNF-α, IL-6, IL-1β, and IL-18) and the antimicrobial peptide CAMP, while also inhibiting NLRP3 inflammasome activation and the TLR4 signaling pathway. Furthermore, TR attenuated LL-37-induced fibrosis and hindered the transforming growth factor-β1 (TGF-β1)/Smad2/3 pathway. In summary, our study underscores TR's therapeutic potential in rosacea by mitigating both skin inflammation and fibrosis, thereby offering a promising treatment avenue for this condition.