2. Academic Validation
  3. miR-146a Inhibits Biofilm-Derived Cutibacterium acnes-Induced Inflammatory Reactions in Human Keratinocytes

miR-146a Inhibits Biofilm-Derived Cutibacterium acnes-Induced Inflammatory Reactions in Human Keratinocytes

  • J Invest Dermatol. 2019 Dec;139(12):2488-2496.e4. doi: 10.1016/j.jid.2019.03.1161.
Rong Zeng 1,  Haoxiang Xu 1,  Yuzhen Liu 1,  Leilei Du 1,  Zhimin Duan 1,  Jianbo Tong 1,  Yanyan He 1,  Qing Chen 2,  Xu Chen 3,  Min Li 4
Affiliations

Affiliations

  • 1 Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, Jiangsu, China.
  • 2 Jiangsu Province Blood Center, Nanjing, Jiangsu, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: chenqing90@yahoo.com.
  • 3 Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, Jiangsu, China. Electronic address: doctor_chx@hotmail.com.
  • 4 Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, Jiangsu, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: limin@pumcderm.cams.cn.
PMID: 31194941 DOI: 10.1016/j.jid.2019.03.1161
Abstract

Acne is a chronic inflammatory skin disorder that often involves the formation of Cutibacterium acnes (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. In this study, 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 the presence of biofilm-derived C. acnes, TLR2 and its downstream NF-kB and MAPK pathways were activated in keratinocytes. Subsequently, miR-146a was upregulated in these cells along with the induction of IL-6, IL-8, and tumor necrosis factor (TNF)-α. Furthermore, our data indicates that miR-146a could directly bind the 3'-untranslated region of IRAK1 and TNF receptor-associated factor 6 (TRAF6) and suppress their expression, leading to an 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 downregulate the production of IL-6, -8, and TNF-α in acne inflammation by inhibiting the TLR2/IRAK1/TRAF6/NF-κB and MAPK pathways.

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