miR-146a inhibits biofilm-derived Cutibacterium acnes induced inflammatory reactions in human keratinocytes

Abstract Acne is a chronic inflammatory skin disorder that often involves the formation of C. acnes biofilms. Several microRNAs (miRNAs) are known to be involved in inflammatory responses. However, it is unknown whether miRNAs play a role in the inflammatory reaction triggered by C. acnes biofilm. Here we investigated the role of miR-146a in biofilm-derived C. acnes induced inflammatory responses. Increased expressions of miR-146a and toll-like receptor (TLR) 2 were detected in acne lesions. In presence of biofilm-derived C. acnes , TLR2 and its downstream NF-kB and mitogen-activated protein kinase (MAPK) pathways were activated in keratinocytes. Subsequently, miR-146a was up-regulated in these cells along with induction of IL-6, IL-8, and TNF-α. Further, our data indicated that miR-146a could directly bind the 3'-untranslated region (3'-UTR) of IL-1 receptor associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6), and suppress their expression, leading to inhibition of biofilm-derived C. acnes induced activation of NF-kB, p38, and Erk1/2 pathways. Overall, our results indicate that biofilm-derived C. acnes induces miR-146a, which can down-regulate the production of IL-6, -8, and TNF-α in acne inflammation by inhibiting TLR2/IRAK1/TRAF6/NF-κB and MAPK pathways.