Adrenocorticotropin hormone stimulates interleukin-18 expression in human HaCaT keratinocytes.
The hypothalamic-pituitary-adrenal (HPA) axis is activated by stress. This involves the production of corticotropin releasing hormone (CRH) with the subsequent release of proopiomelanocortin (POMC) peptides, of which adrenocorticotropin hormone (ACTH) is most important. Although the skin has the capacity to produce CRH and POMC peptides, the immunomodulatory roles of ACTH in skin are yet unknown. IL-18 has been known to affect cells involved in the inflammatory response. In this study, we aimed to identify the regulatory effect of ACTH on IL-18 expression of skin keratinocytes. Exposure of HaCaT cells to ACTH stimulated formation of IL-18 mRNA transcript and its protein products in a dose-dependent manner. Furthermore, we suggest that ACTH-induced IL-18 production is via the caspase-1 activation pathway, as IL-18 production induced by ACTH could be suppressed by caspase-1 inhibitor, and ACTH could increase caspase-1 activity. The effect of ACTH on IL-18 production was blocked by specific inhibitors of p38 kinase (SB203580) or extracellular signal-regulated kinase (ERK) (PD98059). In addition, ACTH-induced rapid phosphorylation of p38 kinase and ERK, and ACTH signaling occurred via melanocortin receptor 1 (MC1R) and receptor 2 (MC2R). These results suggest that ACTH stimulates IL-18 expression in human keratinocytes, which provides an insight into the interaction between ACTH and inflammatory mediators.
Park
Hyun Jeong
HJ
Department of Dermatology, St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. hjpark@catholic.ac.kr
Kim
Hee Jung
HJ
Lee
Jun Young
JY
Cho
Baik Kee
BK
Gallo
Richard L
RL
Cho
Dae Ho
DH
D000324:Adrenocorticotropic Hormone / Q000502:physiology*; D020170:Caspase 1 / Q000502:physiology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000502:physiology; D011979:Receptors, Pituitary Hormone / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D020382:Interleukin-18; D011725:Pyridines; D012333:RNA, Messenger; D011979:Receptors, Pituitary Hormone; C029446:MSH receptor; D000324:Adrenocorticotropic Hormone; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020170:Caspase 1; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one