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Role of PlGF in rheumatoid arthritis. PlGF, predominantly produced by rheumatoid synoviocytes, promotes angiogenesis and stimulates vascular endothelial cell permeability. Newly employed macrophages produce TNF-α and IL-6 when stimulated by PlGF/Flt-1 binding or by contact with activated endothelial cells. TNF-α and IL-6, in turn, further enhance PlGF secretion by macrophages and synoviocytes, and thus create a vicious cycle of inflammation.
