Mast cells as targets of corticotropin-releasing factor and related peptides.
Several inflammatory skin conditions, including atopic dermatitis (AD) and psoriasis, are exacerbated by stress. Recent evidence suggests that crosstalk between mast cells, neurons and keratinocytes might be involved in such exacerbation. Mast cells are distributed widely in the skin, are present in increased numbers in AD and are located in close proximity to substance P- or neurotensin-containing neurons. Corticotropin-releasing factor (CRF), its structurally related peptide urocortin (Ucn) and their receptors are also present in the skin and their levels are increased following stress. Human mast cells synthesize and secrete both CRF and Ucn in response to immunoglobulin E receptor (FcepsilonRI) crosslinking. Mast cells also express CRF receptors, activation of which leads to the selective release of cytokines and other pro-inflammatory mediators. Thus, we propose that CRF receptor antagonists could be used together with natural molecules, such as retinol and flavonoids, to inhibit mast cell activation and provide new therapeutic options for chronic inflammatory conditions exacerbated by stress.
Theoharides
Theoharis C
TC
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA. theoharis.theoharides@tufts.edu
Donelan
Jill M
JM
Papadopoulou
Nikoletta
N
Cao
Jing
J
Kempuraj
Duraisamy
D
Conti
Pio
P
D000818:Animals; D002450:Cell Communication; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011565:Psoriasis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D013312:Stress, Physiological / Q000150:complications / Q000276:immunology
D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone