Induction of human B2 bradykinin receptor mRNA and membrane receptors by IFNγ

A potential mechanism for the increased sensitivity of inflamed tissues to bradykinin is the upregulation of bradykinin receptor expression. We report that recombinant human IFNγ stimulated a concentration-dependent increase in cell surface bradykinin receptor expression in intact T24 human epithelial-like cells, determined by radioligand binding analysis. Analysis of specific [3H]-bradykinin binding revealed that IFNγ-treated cells had a two- to threefold increase in bradykinin receptor number compared to the controls with no effect on receptor affinity. The ability of IFNγ to stimulate increased bradykinin receptor expression was abrogated by treatment with either the transcription inhibitor actinomycin D or the protein synthesis inhibitor cycloheximide. IFNγ enhanced steady-state human B2 bradykinin receptor mRNA expression in the T24 cells in a dose-dependent manner. B2 bradykinin receptor mRNA expression was increased as early as 1 h following IFNγ stimulation, and continued to accumulate for 24 h. Bradykinin-stimulated intracellular calcium mobilization was also increased in IFNγ-treated T24 cells compared to controls. The ability of IFNγ to upregulate B2 bradykinin receptors in primary epithelial cells was demonstrated using cultured human airway epithelial cells. These observations suggest that increasing IFNγ levels during inflammation may upregulate the expression of B2 bradykinin receptors, leading to increased sensitivity to bradykinin.