Pituitary adenylate cyclase-activating polypeptide deficiency enhances oxazolone-induced allergic contact dermatitis in mice.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in capsaicin-sensitive sensory neurons and inflammatory/immune cells, therefore it is suggested to play a role in neuro-immune interactions. Our aim was to investigate the role of PACAP in oxazolone-induced delayed-type hypersensitivity reaction in the skin using deficient mice (PACAP(-/-)). Sensitization was induced by 2% oxazolone application on the shaved abdomen on two consecutive days; inflammation was elicited by oxazolone smearing on the ears 6 days later. Ear thickness was measured by micrometry. Histological examination, cytokine profile [IL-2, IL-4, IL-5, and monocyte chemoattractant protein-1: MCP-1, IFN-γ, tumor necrosis factor alpha (TNF-α)] and myeloperoxidase activity correlating with the number of neutrophils/macrophages were determined 24 and 48 h later. Oxazolone induced a 110-130% swelling after 24-48 h in wild-type mice, which was significantly greater in PACAP-deficient mice. Histological analysis confirmed markedly increased edema in PACAP(-/-) mice, but the moderately enhanced inflammatory cell accumulation was not statistically significant compared with the wild-types. There was no difference in myeloperoxidase activity of the ear homogenates. Elevation of MCP-1, but not the levels of the other cytokines, was significantly higher in the samples of the PACAP-deficient mice. These results suggest that PACAP exerts anti-inflammatory, particularly edema-inhibiting effects in allergic contact dermatitis.
Kemény
Agnes
A
Department of Pharmacology and Pharmacotherapy, University of Pécs, Pécs, Hungary.
Reglodi
Dóra
D
Cseharovszky
Renáta
R
Hashimoto
Hitoshi
H
Baba
Akemichi
A
Szolcsányi
János
J
Pintér
Erika
E
Helyes
Zsuzsanna
Z
D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010081:Oxazolone / Q000276:immunology* / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency* / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000473:pathology
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010081:Oxazolone