The kallikrein-kininogen-kinin system in chronic inflammation.
We examined bradykinin's effects on macrophages and fibroblasts, two cell types important in the pathogenesis of chronic inflammation. Bradykinin stimulated release of proteins of 18 kDa from macrophages. These proteins caused increased thymocyte proliferation (interleukin 1, IL-1) and completely inhibited lipoprotein lipase (tumor necrosis factor, TNF). When fibroblasts were incubated with bradykinin, PGE2 synthesis was stimulated. Pretreatment with IL-1 or TNF dramatically amplified bradykinin-stimulated PGE2 synthesis. Thus, bradykinin is involved in a positive feedback loop in which bradykinin activates macrophages to release potent inflammatory cytokines; these in turn amplify responsiveness of bradykinin target tissues.
Burch
R M
RM
Nova Pharmaceutical Corp., Baltimore, MD 21224.
Connor
J R
JR
Tiffany
C W
CW
D002908:Chronic Disease; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D007375:Interleukin-1 / Q000096:biosynthesis; D007610:Kallikreins / Q000502:physiology*; D007704:Kininogens / Q000502:physiology*; D007705:Kinins / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D007704:Kininogens; D007705:Kinins; D014409:Tumor Necrosis Factor-alpha; D007610:Kallikreins