OPN promotes pro-inflammatory cytokine expression via ERK/JNK pathway and M1 macrophage polarization in Rosacea

Abstract

Abstract Objective: 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. OPN is significantly elevated in the epidermis of rosacea patients. However, the role of OPN in rosacea remains to be elucidated. Methods: OPN knockout mice and WT mice were used to establish LL37-induced rosacea-like skin inflammation models. Histological analyses were performed to detect immune cell infiltration and angiogenesis. In addition, we study the mechanism of OPN in keratinocytes by OPN overexpression or deficiency. The co-culture assay was conducted to investigate keratinocyte-macrophage crosstalk in rosacea inflammation. Results: In this study, it was found that OPN expression was significantly upregulated in rosacea patients and LL37-induced rosacea-like skin inflammation. OPN regulated pro-inflammatorycytokine IL1B and contributed macrophage polarizationtowards M1 phenotype in rosacea-like skin inflammation. In vitro, it was demonstrated that intracellular OPN (iOPN) promoted LL-37-induced IL1B productionthrough ERK1/2 and JNK pathways in keratinocytes . Moreover, secreted OPN (sOPN) played an important role in keratinocyte-macrophage crosstalk. Conclusions: Our findings identified the different roles of sOPN and iOPN in the pathogenesis of rosacea, suggesting that OPN might be a promising therapeutic target in rosacea treatment.