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The role of nitric oxide synthases in pemphigus vulgaris in a mouse model.
Br J Dermatol 2008; 159(1):68-76BJ

Abstract

BACKGROUND

Pemphigus vulgaris (PV) is a blistering autoimmune disease characterized by IgG autoantibodies against desmoglein 3. Nitric oxide synthases (NOS) may contribute to the increase of inflammation in tissues by the generation of nitrotyrosine residues (NTR).

OBJECTIVES

To investigate whether the production of NTR mediated by NOS may participate in the development of inflammation and acantholysis in PV.

METHODS

Mice were pretreated or not with NOS, tyrosine-kinase (TK) or nuclear factor (NF)-kappaB inhibitors, and then injected with PV-IgG. PV manifestations were examined in all mice. The expression of NTR, constitutive NOS (cNOS) [endothelial NOS (eNOS) and neuronal NOS (nNOS)], inducible NOS (iNOS) and NF-kappaB factor were studied in epidermis of mice using immunohistochemical techniques.

RESULTS

After PV-IgG injection, expressions of NTR, iNOS, eNOS and nNOS increased in acantholytic cells, as did nuclear translocation of NF-kappaB in the basal cells of the epidermis. Pretreatment of mice with inhibitors of TK, nNOS and nonselective NOS, completely prevented NTR expression and the clinical and histological findings of PV in mice. TK inhibitor genistein inhibited both nNOS and iNOS expression on the membrane of basal keratinocytes, and nuclear translocation of NF-kappaB.

CONCLUSIONS

Upregulation of cNOS and iNOS, NTR generation and nuclear translocation of NF-kappaB may contribute to increased inflammation and tissue damage in PV lesions. The absence of the clinical and histological findings of PV and NTR expression in mice injected with PV-IgG, through pretreatment with TK and nNOS inhibitors, provides compelling evidence that these signalling molecules should be considered as potential therapeutic targets in PV.

Authors+Show Affiliations

Department of Dermatology, University Clinic of Navarra, School of Medicine, University of Navarra, PO 4209, Pamplona 31080, Spain.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18476963

Citation

Marquina, M, et al. "The Role of Nitric Oxide Synthases in Pemphigus Vulgaris in a Mouse Model." The British Journal of Dermatology, vol. 159, no. 1, 2008, pp. 68-76.
Marquina M, España A, Fernández-Galar M, et al. The role of nitric oxide synthases in pemphigus vulgaris in a mouse model. Br J Dermatol. 2008;159(1):68-76.
Marquina, M., España, A., Fernández-Galar, M., & López-Zabalza, M. J. (2008). The role of nitric oxide synthases in pemphigus vulgaris in a mouse model. The British Journal of Dermatology, 159(1), pp. 68-76. doi:10.1111/j.1365-2133.2008.08582.x.
Marquina M, et al. The Role of Nitric Oxide Synthases in Pemphigus Vulgaris in a Mouse Model. Br J Dermatol. 2008;159(1):68-76. PubMed PMID: 18476963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of nitric oxide synthases in pemphigus vulgaris in a mouse model. AU - Marquina,M, AU - España,A, AU - Fernández-Galar,M, AU - López-Zabalza,M J, Y1 - 2008/07/01/ PY - 2008/5/15/pubmed PY - 2008/10/24/medline PY - 2008/5/15/entrez SP - 68 EP - 76 JF - The British journal of dermatology JO - Br. J. Dermatol. VL - 159 IS - 1 N2 - BACKGROUND: Pemphigus vulgaris (PV) is a blistering autoimmune disease characterized by IgG autoantibodies against desmoglein 3. Nitric oxide synthases (NOS) may contribute to the increase of inflammation in tissues by the generation of nitrotyrosine residues (NTR). OBJECTIVES: To investigate whether the production of NTR mediated by NOS may participate in the development of inflammation and acantholysis in PV. METHODS: Mice were pretreated or not with NOS, tyrosine-kinase (TK) or nuclear factor (NF)-kappaB inhibitors, and then injected with PV-IgG. PV manifestations were examined in all mice. The expression of NTR, constitutive NOS (cNOS) [endothelial NOS (eNOS) and neuronal NOS (nNOS)], inducible NOS (iNOS) and NF-kappaB factor were studied in epidermis of mice using immunohistochemical techniques. RESULTS: After PV-IgG injection, expressions of NTR, iNOS, eNOS and nNOS increased in acantholytic cells, as did nuclear translocation of NF-kappaB in the basal cells of the epidermis. Pretreatment of mice with inhibitors of TK, nNOS and nonselective NOS, completely prevented NTR expression and the clinical and histological findings of PV in mice. TK inhibitor genistein inhibited both nNOS and iNOS expression on the membrane of basal keratinocytes, and nuclear translocation of NF-kappaB. CONCLUSIONS: Upregulation of cNOS and iNOS, NTR generation and nuclear translocation of NF-kappaB may contribute to increased inflammation and tissue damage in PV lesions. The absence of the clinical and histological findings of PV and NTR expression in mice injected with PV-IgG, through pretreatment with TK and nNOS inhibitors, provides compelling evidence that these signalling molecules should be considered as potential therapeutic targets in PV. SN - 1365-2133 UR - https://www.unboundmedicine.com/medline/citation/18476963/The_role_of_nitric_oxide_synthases_in_pemphigus_vulgaris_in_a_mouse_model_ L2 - https://doi.org/10.1111/j.1365-2133.2008.08582.x DB - PRIME DP - Unbound Medicine ER -