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

• Published in: Experimental dermatology Vol. 20; no. 11; pp. 911 - 914
• Main Authors: Orita, Kumi, Hiramoto, Keiichi, Kobayashi, Hiromi, Ishii, Masamitsu, Sekiyama, Atsuo, Inoue, Masayasu
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2011; Blackwell
• Subjects: Adrenocorticotropic Hormone - pharmacology; Allergic diseases; alpha-MSH - pharmacology; alpha-MSH - physiology; Animals; atopic dermatitis; Biological and medical sciences; Dermatitis, Atopic - etiology; Dermatitis, Atopic - immunology; Dermatitis, Atopic - pathology; Dermatitis, Atopic - physiopathology; Dermatology; Disease Models, Animal; Enzyme Inhibitors - pharmacology; Histamine - metabolism; immunoglobulin E; Immunoglobulin E - blood; Immunopathology; inducible nitric oxide synthase; Male; Mast Cells - enzymology; Mast Cells - immunology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; NG-Nitroarginine Methyl Ester - pharmacology; nitric oxide; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - deficiency; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - physiology; Ovalbumin - immunology; Pruritus - etiology; Skin - immunology; Skin - metabolism; Skin allergic diseases. Stinging insect allergies; Transforming Growth Factor beta - pharmacology; Tryptases - metabolism; Tumor Necrosis Factor-alpha - pharmacology; α-melanocyte-stimulating hormone; Immunopathology; Allergy; Skin disease; Immunoglobulins; α-melanocyte-stimulating hormone; Enzyme; Dermatology; Rodentia; Melanocyte stimulating hormone; immunoglobulin E; Nitric-oxide synthase; Atopy; inducible nitric oxide synthase; Vertebrata; Mammalia; Mouse; Atopic dermatitis; Animal; Nitric oxide; Oxidoreductases
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/j.1600-0625.2011.01360.x

:  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)‐β, tumor necrosis factor (TNF)‐α, adrenocorticotropic hormone (ACTH) and α‐melanocyte‐stimulating hormone (α‐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, α‐MSH, ACTH, TGF‐β and TNF‐α were analysed by ELISA. Sensitization of mice with OVA resulted in increased plasma levels of OVA‐IgE, α‐MSH, ACTH, TGF‐β and TNF‐α 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 α‐MSH exhibited a change similar to that seen in the control, whereas iNOS−/− mice given ACTH, TGF‐β or TNF‐α did not demonstrate any changes. These results indicate that symptoms of AD such as scratching can be exacerbated by α‐MSH, which is induced by iNOS‐derived NO.