OPN promotes pro-inflammatory cytokine expression via ERK/JNK pathway and M1 macrophage polarization in Rosacea
Siyi Tang, Hao Hu, Manhui Li, Kaoyuan Zhang, Qi Wu, Xiaojuan Liu, Lin Wu, Bo Yu, Xiaofan Chen
Abstract
Rosacea is a chronic inflammatory dermatosis that involves dysregulation of innate and adaptive immune systems. Osteopontin (OPN) is a phosphorylated glycoprotein produced by a broad range of immune cells such as macrophages, keratinocytes, and T cells. However, the role of OPN in rosacea remains to be elucidated. In this study, it was found that OPN expression was significantly upregulated in rosacea patients and LL37-induced rosacea-like skin inflammation. Transcriptome sequencing results indicated that OPN regulated pro-inflammatory cytokines and promoted macrophage polarization towards M1 phenotype in rosacea-like skin inflammation. In vitro , it was demonstrated that intracellular OPN (iOPN) promoted LL37-induced IL1B production through ERK1/2 and JNK pathways in keratinocytes. Moreover, secreted OPN (sOPN) played an important role in keratinocyte-macrophage crosstalk. In conclusion, sOPN and iOPN were identified as key regulators of the innate immune system and played different roles in the pathogenesis of rosacea.