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Activation of nuclear factor-kappa B and gene expression in human endothelial cells by the common haptens nickel and cobalt.
J Immunol. 1995 Sep 01; 155(5):2459-67.JI

Abstract

Nickel chloride (NiCl2) and cobalt chloride (CoCl2), two haptens frequently leading to contact hypersensitivity in industrialized countries, induce gene transcription of adhesion molecules ICAM-1, VCAM-1, and E-selectin in endothelial cells. In search of transcriptional mechanisms underlying their gene-inductive effects, we studied the capacity of both haptens to activate nuclear factor (NF)-kappa B, a transcription factor involved in inducible expression of adhesion molecules. Using electrophoretic mobility shift assays, a strong increase of NF-kappa B DNA binding was detected after stimulation of HUVEC with NiCl2 or CoCl2. Supershift analysis using antisera against p50 and p65 confirmed the authenticity of the induced NF-kappa B complex. Neutralizing Abs against TNF-alpha and IL-1 did not inhibit metal hapten-induced activation of NF-kappa B, thus ruling out action via an indirect autocrine pathway. In addition, NiCl2-induced activation of NF-kappa B and adhesion molecule expression was inhibited by the antioxidant pyrrolidine dithiocarbamate, indicating the involvement of redox-dependent mechanisms. Furthermore, NiCl2 was found to induce dose-dependency mRNA production and protein secretion of the NF-kappa B-controlled proinflammatory cytokine IL-6. Our data suggest that distinct allergens represent a new class of so far unknown agents that induce NH-kappa B binding activity that subsequently modulates transcription of cytokine and adhesion molecule genes. Thus, pathomechanisms leading to contact hypersensitivity to NiCl2 and CoCl2 appear to involve not only Ag-specific Langerhans- and T cell-dependent events but also include direct effects on other immunocompetent cells such as the endothelium.

Authors+Show Affiliations

Institute of Experimental Dermatology, University of Münster, Germany.No affiliation info availableNo 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

7544377

Citation

Goebeler, M, et al. "Activation of Nuclear Factor-kappa B and Gene Expression in Human Endothelial Cells By the Common Haptens Nickel and Cobalt." Journal of Immunology (Baltimore, Md. : 1950), vol. 155, no. 5, 1995, pp. 2459-67.
Goebeler M, Roth J, Bröcker EB, et al. Activation of nuclear factor-kappa B and gene expression in human endothelial cells by the common haptens nickel and cobalt. J Immunol. 1995;155(5):2459-67.
Goebeler, M., Roth, J., Bröcker, E. B., Sorg, C., & Schulze-Osthoff, K. (1995). Activation of nuclear factor-kappa B and gene expression in human endothelial cells by the common haptens nickel and cobalt. Journal of Immunology (Baltimore, Md. : 1950), 155(5), 2459-67.
Goebeler M, et al. Activation of Nuclear Factor-kappa B and Gene Expression in Human Endothelial Cells By the Common Haptens Nickel and Cobalt. J Immunol. 1995 Sep 1;155(5):2459-67. PubMed PMID: 7544377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of nuclear factor-kappa B and gene expression in human endothelial cells by the common haptens nickel and cobalt. AU - Goebeler,M, AU - Roth,J, AU - Bröcker,E B, AU - Sorg,C, AU - Schulze-Osthoff,K, PY - 1995/9/1/pubmed PY - 1995/9/1/medline PY - 1995/9/1/entrez SP - 2459 EP - 67 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 155 IS - 5 N2 - Nickel chloride (NiCl2) and cobalt chloride (CoCl2), two haptens frequently leading to contact hypersensitivity in industrialized countries, induce gene transcription of adhesion molecules ICAM-1, VCAM-1, and E-selectin in endothelial cells. In search of transcriptional mechanisms underlying their gene-inductive effects, we studied the capacity of both haptens to activate nuclear factor (NF)-kappa B, a transcription factor involved in inducible expression of adhesion molecules. Using electrophoretic mobility shift assays, a strong increase of NF-kappa B DNA binding was detected after stimulation of HUVEC with NiCl2 or CoCl2. Supershift analysis using antisera against p50 and p65 confirmed the authenticity of the induced NF-kappa B complex. Neutralizing Abs against TNF-alpha and IL-1 did not inhibit metal hapten-induced activation of NF-kappa B, thus ruling out action via an indirect autocrine pathway. In addition, NiCl2-induced activation of NF-kappa B and adhesion molecule expression was inhibited by the antioxidant pyrrolidine dithiocarbamate, indicating the involvement of redox-dependent mechanisms. Furthermore, NiCl2 was found to induce dose-dependency mRNA production and protein secretion of the NF-kappa B-controlled proinflammatory cytokine IL-6. Our data suggest that distinct allergens represent a new class of so far unknown agents that induce NH-kappa B binding activity that subsequently modulates transcription of cytokine and adhesion molecule genes. Thus, pathomechanisms leading to contact hypersensitivity to NiCl2 and CoCl2 appear to involve not only Ag-specific Langerhans- and T cell-dependent events but also include direct effects on other immunocompetent cells such as the endothelium. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7544377/Activation_of_nuclear_factor_kappa_B_and_gene_expression_in_human_endothelial_cells_by_the_common_haptens_nickel_and_cobalt_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=7544377 DB - PRIME DP - Unbound Medicine ER -