The role of corticotropin-releasing hormone in immune-mediated cutaneous inflammatory disease.
Corticotropin-releasing hormone (CRH) coordinates the systemic stress response via hypothalamic-pituitary-adrenal (HPA) axis activation with subsequent modulation of the inflammatory response. Stress is known to affect expression of immune-mediated inflammatory diseases, many of which are associated with HPA axis abnormalities. HPA axis components including CRH and its receptors (CRH-R) exist in the skin and exhibit differential expression according to cell type, physiological fluctuations and disease states. This confirms a local functioning cutaneous HPA-like system. Peripheral CRH may exhibit proinflammatory effects. Animal studies confirm that peripheral CRH is required for induction of the inflammatory response in vivo. CRH and CRH-R are upregulated in inflammatory arthritis synovium and psoriatic skin. CRH may influence mast cell activation, direct modulation of immune cells, angiogenesis and induction of the novel orphan nuclear receptor NURR1. This transcription factor is part of the steroid/thyroid superfamily of related nuclear receptors that includes receptors for steroids, retinoids and vitamin D; ligands of these receptors are effective in treating psoriasis. The roles of CRH and NURR1 in psoriasis and inflammatory skin diseases, especially those associated with stress, remain to be elucidated. This stress may be psychological or physical. CRH, produced locally or delivered by peripheral nerves, may mediate interactions between a cutaneous HPA axis-like system and the central HPA axis--the "brain-skin axis".
O'Kane
Marina
M
Department of Dermatology, Adelaide and Meath Hospital, Dublin 24, Ireland. mokdoc@hotmail.com
Murphy
Evelyn P
EP
Kirby
Brian
B
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000276:immunology / Q000502:physiology*; D003872:Dermatitis / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013312:Stress, Physiological / Q000276:immunology / Q000503:physiopathology
D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone