title: The role of calcitonin gene-related peptide in cutaneous immunosuppression induced by repeated subinflammatory ultraviolet irradiation exposure.
abstract: Ultraviolet (UV) light is an effective treatment for skin disorders like psoriasis in which the cutaneous neurosensory system may have a pathogenic role. In this study, we examined the possibility that UV modulation of the cutaneous neurosensory system and calcitonin gene-related peptide (CGRP) may contribute to local immunosuppression mediated by repeated subinflammatory UV irradiation. Our results indicated that exposure of hairless mice to subinflammatory UV three times weekly for 4 weeks significantly increased the number of epidermal nerve fibers (ENFs) immunoreactive for CGRP without altering the total number of ENFs. The skin content of CGRP as measured by enzyme-linked immunosorbent assay was also significantly increased after exposure to this dose of UV. These effects were most apparent 1 day after the last UV exposure and declined 1 week after UV. The role of CGRP in UV-induced immunosuppression of contact hypersensitivity was then examined. Our results indicated that UV suppression of epicutaneous 2,4-dinitro-1-fluorobenzene (DNFB) sensitization could be significantly inhibited by a systemically administered CGRP receptor antagonist. A broad-spectrum sunscreen applied before UV exposure inhibited increased cutaneous CGRP and blocked immunosuppression. These findings support a role for CGRP in the local immunosuppression caused by chronic, repeated subinflammatory UV exposure.
authors.affiliation: Department of Dermatology, Emory University, School of Medicine, Atlanta, GA, USA. franz.legat@meduni-graz.at
authors.forename: Franz J
authors.initials: FJ
authors.lastname: Legat
authors.forename: Lasha T
authors.initials: LT
authors.lastname: Jaiani
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
authors.forename: Minsheng
authors.initials: M
authors.lastname: Wang
authors.forename: Roland
authors.initials: R
authors.lastname: Lang
authors.forename: Tonya
authors.initials: T
authors.lastname: Abraham
authors.forename: Alvin R
authors.initials: AR
authors.lastname: Solomon
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Armstrong
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Glass
authors.forename: John C
authors.initials: JC
authors.lastname: Ansel
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D007108:Immune Tolerance / Q000528:radiation effects; D051379:Mice; D008812:Mice, Hairless; D009412:Nerve Fibers / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D012867:Skin / Q000276:immunology* / Q000294:innervation / Q000378:metabolism / Q000528:radiation effects*; D013373:Substance P / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D013373:Substance P; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide