Abstract:

Objective To investigate the mechanism of minocycline in acne Inflammation by regulating peroxisome proliferator-activated receptor γ （PPARγ）/STAT3 signaling pathway. Methods An acne-like model was established by intradermal injection of Cutibacterium acnes into mice， followed by oral administration of minocycline or sterile water. Skin lesions were observed， and hematoxylin?eosin staining， immunohistochemistry， and immunofluorescence were performed to assess inflammatory cell infiltration and pathway-related factor expression. In parallel， SZ95 human sebocytes were stimulated with peptidoglycan （PGN） and treated with minocycline， with or without the PPARγ antagonist T0070907. Inflammatory cytokines （IL-1α， IL-1β， IL-6， IL-8） were quantified， and PPARγ and STAT3 expression were analyzed. Results Minocycline treatment significantly alleviated skin inflammation in mice， reduced inflammatory cell infiltration， enhanced PPARγ expression， decreased IL-1β and MPO-positive cells， and significantly attenuated p-STAT3 immunoreactivity （P < 0.05）. In SZ95 sebocytes， PGN induced robust cytokine production and STAT3 phosphorylation. Minocycline treatment significantly suppressed pro-inflammatory cytokines， upregulated PPARγ， and inhibited STAT3 activation， whereas the presence of T0070907 partially reversed these effects. Conclusions Minocycline exerts anti-inflammatory effects in acne by activating the PPARγ/STAT3 pathway， thereby dampening cytokine release and neutrophil infiltration. These findings highlight PPARγ as a potential therapeutic target and provide mechanistic insight into the anti-inflammatory benefits of minocycline in acne management.

Key words: acne vulgaris, minocycline, PPARγ, inflammatory cytokines, sebocytes