title: Corticotropin-releasing hormone (CRH) downregulates interleukin-18 expression in human HaCaT keratinocytes by activation of p38 mitogen-activated protein kinase (MAPK) pathway.
abstract: 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 pre-treatment 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.
authors.affiliation: Department of Dermatology, St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Baik Kee
authors.initials: BK
authors.lastname: Cho
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
authors.forename: Hyungsik
authors.initials: H
authors.lastname: Kang
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Cho
mesh_terms: D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D000078404:Epidermal Cells; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D020382:Interleukin-18; D003346:Corticotropin-Releasing Hormone; D048051:p38 Mitogen-Activated Protein Kinases