Bradykinin stimulates eotaxin production by a human lung fibroblast cell line.
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 fibro-blasts 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.


CONCLUSIONS
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.
Sato
E
E
Research Service, Southern Arizona Veterans Health Care System, and the Department of Medicine, University of Arizona, Tucson, USA.
Nelson
D K
DK
Koyama
S
S
Hoyt
J C
JC
Robbins
R A
RA
D001920:Bradykinin / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002460:Cell Line; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007106:Immune Sera; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D065168:Bradykinin Receptor Antagonists; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D007106:Immune Sera; D007375:Interleukin-1; D012333:RNA, Messenger; D003907:Dexamethasone; D001920:Bradykinin