RIP4 upregulates CCL20 expression through STAT3 signalling in cultured keratinocytes

Hyun Cheol Bae, Sang Hoon Jeong, Jin Hee Kim, Hana Lee, Woo In Ryu, Min Gyu Kim, Eui Dong Son, Tae Ryong Lee, Sang Wook Son

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The receptor-interacting protein kinase 4 (RIP4), a serine/threonine kinase, is an important modulator of epidermal growth and cutaneous inflammation. We found that RIP4 expression was significantly increased in the lesional skin of psoriasis. However, the role and regulatory mechanism of RIP4 in psoriasis have not been characterized. After treatment with IL-17, RIP4 mRNA and protein levels were increased in HaCaT cells. IL-17 also activated the RIP4 promoter. To understand the functional role of RIP4 in keratinocyte and to investigate the genes regulated by RIP4, RNA-based microarray analysis was performed. Among immune response-related genes, CCL20 expression was significantly changed by RIP4. To identify RIP4-interacting protein, an immunoprecipitation assay was performed. As a result, STAT3 was identified as a new protein that interacts with RIP4. The interaction of RIP4 and STAT3 enhanced STAT3 phosphorylation. In addition, the transcriptional activity of STAT3 induced by RIP4 regulated IL-17-mediated CCL20 expression in HaCaT cells. Taken together, these findings indicate that IL-17 increased RIP4-mediated STAT3 phosphorylation by directly interacting with STAT3. Thus, transcriptional activation of STAT3 promotes the expression of CCL20. Thus, activations of these signalling pathways by RIP4 may contribute to epithermal inflammation in psoriatic keratinocytes.

Original languageEnglish
JournalExperimental Dermatology
DOIs
Publication statusAccepted/In press - 2018 Jan 1

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Keywords

  • CCL20
  • IL-17
  • Keratinocytes
  • RIP4
  • STAT3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Bae, H. C., Jeong, S. H., Kim, J. H., Lee, H., Ryu, W. I., Kim, M. G., Son, E. D., Lee, T. R., & Son, S. W. (Accepted/In press). RIP4 upregulates CCL20 expression through STAT3 signalling in cultured keratinocytes. Experimental Dermatology. https://doi.org/10.1111/exd.13750