Inducible nitric oxide synthase (iNOS) and α-melanocyte-stimulating hormones of iNOS origin play important roles in the allergic reactions of atopic dermatitis in mice

To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we used an animal model of atopic dermatitis (AD) induced by epicutaneous sensitization and analysed the differences in ear thickness, the frequency of scratching and plasma levels of ovalbumin-specific immunoglobulin E (OVA-IgE), transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) between control and iNOS(-/-) mice. Eight-week-old control and iNOS(-/-) male C57BL/6j mice were sensitized three times with OVA antigen. Before and after the last skin sensitization, the number of scratching incidents and the thickness of the ear were examined, and the plasma levels of OVA-IgE, alpha-MSH, ACTH, TGF-beta and TNF-alpha were analysed by ELISA. Sensitization of mice with OVA resulted in increased plasma levels of OVA-IgE, alpha-MSH, ACTH, TGF-beta and TNF-alpha in control, but not in iNOS(-/-) mice. The administration of L-nitro-arginine-methyl ester (L-NAME) abolished all the above changes that occurred in the control mice. In addition, iNOS(-/-) mice given alpha-MSH exhibited a change similar to that seen in the control, whereas iNOS(-/-) mice given ACTH, TGF-beta or TNF-alpha did not demonstrate any changes. These results indicate that symptoms of AD such as scratching can be exacerbated by alpha-MSH, which is induced by iNOS-derived NO.