The role of calcitonin gene-related peptide in cutaneous immunosuppression induced by repeated subinflammatory ultraviolet irradiation exposure.
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.
Legat
Franz J
FJ
Department of Dermatology, Emory University, School of Medicine, Atlanta, GA, USA. franz.legat@meduni-graz.at
Jaiani
Lasha T
LT
Wolf
Peter
P
Wang
Minsheng
M
Lang
Roland
R
Abraham
Tonya
T
Solomon
Alvin R
AR
Armstrong
Cheryl A
CA
Glass
Jonathan D
JD
Ansel
John C
JC
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
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D013373:Substance P; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide