DIFFERENTIAL EXPRESSION OF NITRIC OXIDE SYNTHASES IN THE SKIN TISSUE OF P-PHENYLENEDIAMINE-TREATED MICE
Objective: p-Phenylenediamine (PPD) is a possible contact sensitizer in skin tissues; however, data are lacking regarding its specific effects on nitric oxide synthase (NOS) expression during the sensitization phase. The purpose of this study was to investigate nNOS and iNOS expression in the skin tissue of PPD-treated mice.
Methods: BALB/c mice were dermally exposed to PPD, at a dose of 10 or 50 mg/kg, on three occasions. The ear and dorsal skin tissues were then isolated from PPD-treated mice and vehicle-treated controls. Western blot analyses were performed on samples derived from the skin tissues.
Results: The dorsal skin tissues of PPD-treated BALB/c mice showed significantly increased levels of iNOS. However, nNOS expression in dorsal skin, and nNOS and iNOS expression in the ear, was not significantly altered in PPD-treated skin tissues compared to controls.
Conclusion: Because enhanced expression of iNOS may contribute to inflammation in allergic contact dermatitis, our data suggest that increased levels of iNOS may be involved in early immunological responses to PPD-induced pathogenesis in dorsal skin.
2. Thyssen JP, White JM. Epidemiological data on consumer allergy to p-phenylenediamine. Contact Dermatitis 2008;59:327-43.
3. LaBerge L, Pratt M, Fong B, Gavigan G. A 10-year review of p-phenylenediamine allergy and related para-amino compounds at the ottawa patch test clinic. Dermatitis 2011;22:332-4.
4. Pot LM, Scheitza SM, Coenraads PJ, BlÃ¶meke B. Penetration and haptenation of p-phenylenediamine. Contact Dermatitis 2013;68:193-207.
5. SÃ¸sted H, Agner T, Andersen KE, MennÃ© T. 55 cases of allergic reactions to hair dye: a descriptive, consumer complaint-based study. Contact Dermatitis 2002;47:299-303.
6. Farrell J, Jenkinson C, Lavergne SN, Maggs JL, Kevin Park B, Naisbitt DJ. Investigation of the immunogenicity of p-phenylenediamine and Bandrowski's base in the mouse. Toxicol Lett 2009;185:153-9.
7. Pot LM, Coenraads PJ, Goebel C, BlÃ¶meke B. Assessment of the elicitation response in subjects weakly sensitized to p-phenylenediamine. Br J Dermatol 2015;172:138-44.
8. Sahin S, Onder M, Sancak B, Bukan N, GÃ¼rer MA. The role of nitric oxide in allergic contact dermatitis. Arch Dermatol Res 2001;293:214-7.
9. Cruz MT, Neves BM, GonÃ§alo M, Figueiredo A, Duarte CB, Lopes MC. Effect of skin sensitizers on inducible nitric oxide synthase expression and nitric oxide production in skin dendritic cells: role of different immunosuppressive drugs. Immunopharmacol Immunotoxicol 2007;29:225-41.
10. Knowles RG, Moncada S. Nitric oxide synthases in mammals. Biochem J 1994;298:249-58.
11. Abramson SB, Amin AR, Clancy RM, Attur M. The role of nitric oxide in tissue destruction. Best Pract Res Clin Rheumatol 2001;15:831-45.
12. Weller R. Nitric oxide: a key mediator in cutaneous physiology. Clin Exp Dermatol 2003;28:511-4.
13. Bredt DS, Glatt CE, Hwang PM, Fotuhi M, Dawson TM, Snyder SH. Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neurons 1991;7:615-24.
14. Yuan T, Vogel HJ, Sutherland C, Walsh MP. Characterization of the Ca2+-dependent and-independent interactions between calmodulin and its binding domain of inducible nitric oxide synthase. FEBS Lett 1998;431:210-4.
15. Nakai K, Fujii S, Yamamoto A, Igarashi J, Kubota Y, Kosaka H. Effects of high glucose on NO synthesis in man keratinocyte cell line (HaCaT). J Dermatol Sci 2003;31:211-8.
16. Bruch-Gerharz D, Ruzicka T, Kolb-Bachofen V. Nitric oxide in human skin: current status and future prospects. J Invest Dermatol 1998;110:1-7.
17. Cals-Grierson MM, Ormerod AD. Nitric oxide function in the skin. Nitric Oxide 2004;10:179-93.
18. Nishioka Y, Wen H, Mitani K, Robbins PD, Lotze MT, Sone S, et al. Differential effects of IL-12 on the generation of alloreactive CTL mediated by murine and human dendritic cells: a critical role for nitric oxide. J Leukocyte Biol 2003;73:621-9.
19. Marquina M, EspaÃ±a A, FernÃ¡ndez-Galar M, LÃ³pez-Zabalza MJ. The role of nitric oxide synthases in pemphigus vulgaris in a mouse model. Br J Dermatol 2008;159:68-76.
20. Ikeyama K, Denda S, Tsutsumi M, Denda M. Neuronal nitric oxide synthase in epidermis is involved in cutaneous circulatory response to mechanical stimulation. J Invest Dermatol 2010;130:1158-66.
21. Svalgaard JD, SÃ¦rmark C, Dall M, Buschard K, Johansen JD, Engkilde K. Systemic immunogenicity of para-phenylenediamine and diphenylcyclopropenone: two potent contact allergy-inducing haptens. Immunol Res 2014;58:40-50.
22. Schwentker A, Vodovotz Y, Weller R, Billiar TR. Nitric oxide and wound repair: role of cytokines? Nitric Oxide 2002;7:1-10.
23. RomÃ©ro-Graillet C, Aberdam E, ClÃ©ment M, Ortonne JP, Ballotti R. Nitric oxide produced by ultraviolet-irradiated keratinocytes stimulates melanogenesis. J Clin Invest 1997;99:635-42.
24. Bruch-Gerharz D, Fehsel K, Suschek C, Michel G, Ruzicka T, Kolb-Bachofen V. A proinflammatory activity of interleukin 8 in human skin: expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes. J Exp Med 1996;184:2007-12.
25. BÃ©cherel PA, Chosidow O, Le Goff L, FrancÃ¨s C, DebrÃ© P, Mossalayi MD, et al. Inducible nitric oxide synthase and proinflammatory cytokine expression by human keratinocytes during acute urticaria. Mol Med 1997;3:686-94.
26. Rowe A, Farrele AM, Bunker CB. Constitutive endothelial and inducible nitric oxide synthase in inflammatory dermatoses. Br J Dermatol 1997;136:18-23.
27. Teixeira MM, Williams TJ, Hellewell PG. Role of prostaglandins and nitric oxide in acute inflammatory reactions in guinea-pig skin. Br J Pharmacol 1993;110:1515-21.
28. Frank S, Madlener M, Pfeilschifter J, Werner S. Induction of inducible nitric oxide synthase and its corresponding tetrahydrobiopterin-cofactor-synthesizing enzyme GTP- cyclohydrolase I during cutaneous wound repair. J Invest Dermatol 1998;111;1058-64.
29. Ormerod AD, Dwyer CM, Reid A, Copeland P, Thompson WD. Inducible nitric oxide synthase demonstrated in allergic and irritant contact dermatitis. Acta Derm Venereol 1997;77:436-40.
30. Ormerod AD, Weller R, Copeland P, Benjamin N, Ralston SH, Grabowksi P, et al. Detection of nitric oxide and nitric oxide synthases in psoriasis. Arch Dermatol Res 1998;290:3-8.
31. Tsukazaki N, Watanabe M, Shimizu K, Hamasaki Y, Katayama I. Photoprovocation test and immunohistochemical analysis of inducible nitric oxide synthase expression in patients with Sjogrenâ€™s syndrome associated with photosensitivity. Br J Dermatol 2002;147:1102-8.
32. Hara K, Matsuoka T, Hara T, Wakabayashi K, Kanda M, Ando R, et al. Useful method for evaluation of local irritation using auricular subcutis of rabbits. J Toxicol Sci 2012;37:197-205.