Induction of human B2 bradykinin receptor mRNA and membrane receptors by IFNgamma.
A potential mechanism for the increased sensitivity of inflamed tissues to bradykinin is the upregulation of bradykinin receptor expression. We report that recombinant human IFNgamma 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 IFNgamma-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 IFNgamma to stimulate increased bradykinin receptor expression was abrogated by treatment with either the transcription inhibitor actinomycin D or the protein synthesis inhibitor cycloheximide. IFNgamma 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 IFNgamma stimulation, and continued to accumulate for 24 h. Bradykinin-stimulated intracellular calcium mobilization was also increased in IFNgamma-treated T24 cells compared to controls. The ability of IFNgamma to upregulate B2 bradykinin receptors in primary epithelial cells was demonstrated using cultured human airway epithelial cells. These observations suggest that increasing IFNgamma levels during inflammation may upregulate the expression of B2 bradykinin receptors, leading to increased sensitivity to bradykinin.
Lung
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CC
W.M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jagels
M A
MA
Daffern
P J
PJ
Tan
E M
EM
Zuraw
B L
BL
D001920:Bradykinin / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000096:biosynthesis*; D011994:Recombinant Proteins; D013268:Stimulation, Chemical; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015854:Up-Regulation
D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D011994:Recombinant Proteins; D007371:Interferon-gamma; D001920:Bradykinin; D002118:Calcium