Bradykinin stimulates eotaxin production by a human lung fibroblast cell line

Abstract

Background: Bradykinin, a potent inflammatory peptide, is increased in the airways of allergic patients. Accompanying the elevated bradykinin levels are increases in both eosinophils and fibroblasts. Eotaxin, a potent eosinophil-specific chemotactic factor, is released by fibroblasts and increased in the lower respiratory tract of allergic patients Objective: We sought to test the hypothesis that lung fibroblasts release eotaxin in response to bradykinin. Methods: The potential of bradykinin to induce the release of eotaxin from the human lung fibroblast cell line HFL-1 was tested by cell culture and evaluation of the culture supernatant fluids and RNA for immunoreactive eotaxin and eotaxin messenger RNA. Results: HFL-1 cells released eotaxin constitutively without stimulation, but bradykinin stimulated eotaxin release in a dose- and time-dependent manner and resulted in augmented expression of eotaxin messenger RNA. The release of eotaxin was sensitive to the action of glucocorticoids. Eosinophil chemotactic activity by HFL-1 supernatant fluids was inhibited by anti-human eotaxin-neutralizing antibody. Consistent with these results, inhibitors of bradykinin B2 receptors, but not bradykinin B1 receptors, inhibited bradykinin-induced eotaxin release. Conclusion: These data demonstrate that bradykinin may stimulate lung fibroblasts to release eotaxin and suggest the potential for this mechanism to be important in modulation of lung inflammation.