Regulation of kinin B2 receptors by bradykinin in human lung cells

Abstract

AbstractBradykinin is a potent mediator of inflammation that has been shown to participate in allergic airway inflammation. The biologic effects of bradykinin are mediated by binding and activation of its cognate receptor, the B2receptor (B2R). In the lung fibroblast cell line IMR-90, binding of bradykinin to B2R triggers down-regulation of receptor surface expression, suggesting that bradykinin-induced inflammation is transient and self-limited. Notably, subjects with chronic airway inflammation continue to respond to BK following a first challenge. B2Rs are expressed on many different lung cell types, including airway epithelial cells. We therefore compared IMR-90 cells with the human lung epithelial cell line BEAS2B and found that B2R expression in the two cell types is differently regulated by BK. Whereas BK induces down-regulation of B2R in IMR-90 cells, the same treatment leads to up-regulation of the receptor in BEAS2B cells. These results provide a possible explanation for the potency of bradykinin in inducing ongoing airway inflammation.