Journal article

Publication year: 1999

Pages: 125-142

Journal: Veterinary Immunology and Immunopathology

Volume number: 71

Issue number: 2

ISSN: 0165-2427

DOI Link: https://doi.org/10.1016/S0165-2427(99)00097-5

Publisher: Elsevier

Abstract: 
The cytokine tumor necrosis factor-alpha (TNF-alpha) plays a major role in inflammatory and immune-pathological reactions of the skin. With respect to a possible therapeutic modulation of TNF-alpha mediated activation of Nuclear Factor-kappa B (NF-kappa B) in canine cutaneous inflammation, we investigated the role of NF-kappa B and the involvement of reactive oxygen species (ROS) in the TNF-alpha signalling pathway in dermal fibroblasts of the dog. TNF-alpha treatment resulted in the activation of NF-kappa B as assessed by electrophoretic mobility shift assay (EMSA). Additionally, NF-kappa B translocation was induced with butylhydroperoxide and antimycin A, but not with hydrogen peroxide. TNF-alpha stimulated NF-kappa B activation was partially inhibited by preincubation with the antioxidants alpha-lipoic acid and butylated hydroxyanisol (BHA). No superoxide generation following TNF-alpha stimulation could be detected in the supernatant of canine fibroblasts with the superoxide dismutase-inhibitable cytochrome c reduction test. In contrast, production of TNF-alpha dependent intracellular hydrogen peroxide, the dismutation product of the superoxide radical, was demonstrated spectroscopically by Formation of electron dense cerium-hydroperoxide precipitates. With electron energy loss spectroscopy (EELS) significant cerium deposits were detected in the mitochondria, the endoplasmatic reticulum, the cytosol and to a lesser extent on the plasma membrane of canine fibroblasts indicating multiple hydrogen peroxide production sites. Peroxides, therefore, possibly play an important part in the redox-sensitive pathway of TNF-alpha dependent NF-kappa B activation in canine skin. An adjunctive therapy with appropriate antioxidants modulating NF-kappa B overactivation in cutaneous inflammation in the dog is promising. (C) 1999 Elsevier Science B.V. All rights reserved.

Harvard Citation style: Kohler, H., Knop, J., Martin, M., de Bruin, A., Huchzermeyer, B., Lehmann, H., et al. (1999) Involvement of reactive oxygen species in TNF-alpha mediated activation of the transcription factor NF-kappa B in canine dermal fibroblasts, Veterinary Immunology and Immunopathology, 71(2), pp. 125-142. https://doi.org/10.1016/S0165-2427(99)00097-5

APA Citation style: Kohler, H., Knop, J., Martin, M., de Bruin, A., Huchzermeyer, B., Lehmann, H., Kietzmann, M., Meier, B., & Nolte, I. (1999). Involvement of reactive oxygen species in TNF-alpha mediated activation of the transcription factor NF-kappa B in canine dermal fibroblasts. Veterinary Immunology and Immunopathology. 71(2), 125-142. https://doi.org/10.1016/S0165-2427(99)00097-5