Effect of interferon-γ on inflammatory cytokine-induced bradykinin B1 receptor expression in human vascular cells

Authors: Koumbadinga, Gérémy Abdull; Désormeaux, Anick; Adam, Albert; Marceau, François
Abstract: The expression of the bradykinin B1 receptor is strongly regulated in vascular tissue following injury, with little or no expression in healthy tissues. The present work aimed to verify whether primary human vascular cells (umbilical vein endothelial cells, umbilical artery smooth muscle cells) respond to tumor necrosis factor (TNF)-α and interferon (IFN)-γ by an upregulation of B1 receptors and whether these pathways interact. B1 receptor expression was quantified using a [3H]Lys-des-Arg9-bradykinin binding assay (cell surface protein) and RT-PCR (mRNA). A pharmacological approach exploiting several inhibitory drugs related to cytokine signaling was applied. The combined treatment with TNF-α and IFN-γ had a synergistic effect on B1 receptor expression in both cell types, increasing primarily receptor abundance in both cell types (16 h) and mRNA concentration (4 h) in endothelial cells. The synergistic effect of the IFN-γ–TNF-α combination was abated by drugs targeted at the signaling of either cytokine (for TNF-α: etanercept or the IκB kinase 2 inhibitor TPCA-1; for IFN-γ: neutralizing antibodies to IFN-γ, a pan-Jak inhibitor but not the Jak2 inhibitor AG490). Thus, Jak2 signaling may not be recruited by the IFN-γ receptors in vascular cells; however, Stat1 phosphorylation was correlated as expected to the effect of IFN-γ on B1 receptor expression. Random migration was inhibited by the B1 receptor agonist Lys-des-Arg9-bradykinin only in smooth muscle cells pretreated with the cytokine combination. The amplificatory effect of IFN-γ on TNF-α-induced bradykinin B1 receptor expression is relevant to vasculopathies associated with T helper 1 cytokines.
Document Type: Article de recherche
Issue Date: 31 August 2010
Open Access Date: 17 November 2017
Document version: AM
Permalink: http://hdl.handle.net/20.500.11794/15873
This document was published in: European journal of pharmacology, Vol. 647 (1-3), 117-125 (2010)
Alternative version: 10.1016/j.ejphar.2010.08.008
Collection:Articles publiés dans des revues avec comité de lecture

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