Frontiers in Immunology (Jan 2024)

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

DOI
https://doi.org/10.3389/fimmu.2023.1285951
Journal volume & issue
Vol. 14

Abstract

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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.

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