Minocycline inhibits rosacea-like inflammation through the TLR4-mediated NF-κB signaling pathway in vivo and in vitro.

BACKGROUND: Rosacea is a chronic inflammatory skin disease characterized by multiple intricate pathogenic factors. Previous studies have substantiated the anti-inflammatory properties of minocycline and its potential therapeutic efficacy in treating rosacea. However, further elucidation of the underlying mechanism is warranted. METHODS: HaCaT cells and BALB/c mice were treated with LL37. Moreover, the effect of minocycline on rosacea was explored through the addition of an NF-κB inhibitor (PDTC) or overexpression of Toll-like receptor 4 (TLR4). The expression of related markers was detected by western blotting, immunofluorescence, ELISA, flow cytometry, etc. RESULTS: Minocycline suppressed dermal infiltration of inflammatory cells in rosacea-like mice and reduced the expression of inflammatory cytokines in rosacea-like mice and cells. Moreover, minocycline downregulated the expression of TLR4 and p-NF-κB thereby inhibiting ROS production. However, overexpression of TLR4 or the addition of PDTC counteracted the effects of minocycline by promoting cellular inflammation and ROS production. Mechanistically, minocycline hinders TLR4/TNF-α activation induced by LL37 in skin and cells to suppress the expression of inflammatory cytokines. CONCLUSION: Minocycline alleviates inflammation progression in rosacea by downregulating TLR4 and inhibiting the activation of the NF-κB pathway, providing a scientific basis for subsequent clinical treatment.