Corticotropin-releasing hormone (CRH) downregulates interleukin-18 expression in human HaCaT keratinocytes by activation of p38 mitogen-activated protein kinase (MAPK) pathway

Hyun Jeong Park, Hee Jung Kim, Jung Hoon Lee, Jun Young Lee, Baik Kee Cho, Jae Seung Kang, Hyungsik Kang, Young Yang, Dae Ho Cho

Research output: Contribution to journalArticle

47 Citations (Scopus)


It is generally accepted that corticotropin-releasing hormone (CRH) acts as the main coordinator of the central response to stress. Stress or an abnormal response to stressors has been found to modify the evolution of skin disorders, including psoriasis and atopic dermatitis. Nevertheless, the specific pathogenic role of stress remains unknown in skin diseases. Interleukin (IL)-18, a member of the IL-1 family, is a key mediator of peripheral inflammation and host defense responses, and is secreted by human keratinocytes. Here, we investigated the regulatory effect of CRH on expression of IL-18 in skin keratinocytes. Exposure of HaCaT cells to CRH resulted in a reduction of IL-18 mRNA transcripts and its production was in a concentration-dependent manner. In order to investigate whether the mitogen-activated protein kinase (MAPK) signaling pathway is involved in the downregulation of IL-18 production, cells were pre-treated with SB203580, an inhibitor of p38 MAPK, prior to the addition of CRH. This pretreatment blocked the decrease in IL-18 production. In addition, CRH treatment induced rapid phosphorylation of p38 MAPK. SB203580 were able to inhibit CRH-induced p38 MAPK phosphorylation. CRH also inhibited production of IL-18 in human primary keratinocytes. These results suggest that CRH regulates IL-18 production through the MAPK signaling pathway in human keratinocytes.

Original languageEnglish
Pages (from-to)751-755
Number of pages5
JournalJournal of Investigative Dermatology
Issue number4
Publication statusPublished - 2005 Jan 1
Externally publishedYes



  • Corticotropin-releasing hormone (CRH)
  • Interleukin 18 (IL-18)
  • p38 mitogen-activated protein kinase (p38 MARK)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this