907 Propionibacterium acnes and peptidoglycan reduce lipidgenesis and change differentiation of SZ95 human sebocytes in vitro via aryl hydrocarbon receptor

Individual lesions in acne vulgaris exist spontaneous remission, which is related to shrunken and de-differential sebaceous gland (SGs) in comedone with unknown mechanisms. P. acnes stimulated by increased lipids from SGs plays key role in acne pathogenesis, while the relationship between the P. acnes and SGs is still a myth. We explored the action of P. acnes and peptidoglycan (PGN) on the effects of lipidgenesis and differentiation of cultured SZ95 human sebocytes. Firstly, we observed that both formaldehyde-inactivated P. acnes and PGN reduced Linoleic acid (LA) induced neutral lipid synthesis in SZ95 sebocytes, and GSEA analysis showed that the pathways of lipogenesis were downregulated ,but the pathways of keratinization were upregulated after P. acnes and PGN treatment respectively. Furthermore, expressions of keratin 7 and MUCIN1/EMA, markers of sebocytes differentiation, were decreased, while the terminal keratinocytes differentiation markers keratin 10 and involucrin were increased after P. acnes and PGN stimulation. Meanwhile, we also found P. acnes and PGN inhibit expressions of sebaceous differentiation-related antigens SREBP-1, FAS and PPAR-α. In addition, we proved both P. acnes and PGN could upregulate mRNA expression of CYP1A1, as well as a significantly induced translocation of AhR protein from cytoplasm into nucleus . after knocking out AhR gene the P. acnes and PGN induced changes of neutral lipid synthesis and related genes expressions in SZ95 were normalized. Our data proved evidences that P. acnes could reduce lipid synthesis and change differentiation of SZ95 sebocytes in vitro via activation of AhR signaling pathway, which is not only a motivator of acne initiation, but also a factor of acne remission.