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Corticotropin-releasing hormone (CRH) downregulates interleukin-18 expression in human HaCaT keratinocytes by activation of p38 mitogen-activated protein kinase (MAPK) pathway.
Park HJ, Kim HJ, Lee JH, Lee JY, Cho BK, Kang JS, Kang H, Yang Y, Cho DH.
Department of Dermatology, St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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.
http://www.ncbi.nlm.nih.gov/pubmed/15816833
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Neuroimmune Interactions
ReplyDeleteEffects of Continuous Infusion of Interleukin 1β on Corticotropin-Releasing Hormone (CRH), CRH Receptors, Proopiomelanocortin Gene Expression and Secretion of Corticotropin, β-Endorphin and Corticosterone
Stéphane Mélik Parsadaniantza, Eric Batschéa, Pascale Gegout-Pottieb, Bernard Terlainb, Pierre Gilletb, Patrick Netterb, Bernard Kerdelhuéa
Laboratoire de Neuroendocrinologie, URA 1310 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques, Paris;
Laboratoire de Pharmacologie, URA 1288 CNRS, Faculté de Médecine de Nancy, Vandæuvre, France
Abstract
A number of recent studies suggest that interleukin 1β (IL-1β) is a major mediator of hypothalamo-pituitary-adrenal (HPA) responses following infectious aggression. We investigated whether IL-1β mediates long-term changes in HP A activity and studied the cellular regulation of the anterior pituitary. To mimic chronically elevated IL-1β production thought to occur during infectious diseases, osmotic pumps (Alzet type) were implanted in the peritoneal cavity of male rats and hIL-1β was infused continuously at rates of 1 or 3 μg/day. Effects of hIL-1β action on plasma ACTH, β-endorphin (β-EP) and corticosterone (CORT) secretion and on anterior pituitary (AP), ACTH and β-EP content were followed. In addition, hypothalamic (HT) CRH mRNA and in AP, CRH receptor (CRH-Rc) mRNA, POMC nuclear primary transcript RNA, POMC nuclear intermediate processing RNA and POMC nuclear and cytoplasmic mRNA were quantified using a highly sensitive solution hybridization nuclease protection assay. Continuous infusion of hIL-1 β stimulated the HPA axis at varying degrees. Increased HT CRH gene expression, AP POMC gene transcription, ACTH and β-EP release occurred only during the first 3 days of the treatment. A long-lasting enhancement of ACTH and β-EP synthesis and of POMC gene expression resulted from activated POMC gene transcription followed by an increased POMC mRNA stability and decreased POMC mRNA turnover.
In the AP, stimulation of ACTH and β-EP secretion and POMC gene transcription disappeared after continuous IL-1β treatment, possibly in part due to a refractory process mediated by decreased CRH-Rc gene expression in corticotropes.
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