Reciprocal induction of tumor necrosis factor-? and interleukin-? activity mediates fibronectin synthesis in coronary artery smooth muscle cells

Publisher Website
Google Scholar
Abstract
We previously demonstrated an immune-inflammatory response associated with increased expression of interleukin (IL)-β and fibronectin in graft coronary arteriopathy in piglets following heterotopic heart transplant. Further studies showed that increased endogenously produced IL-β was upregulating fibronectin production by donor coronary artery (CA) smooth muscle cells (SMC). Since co-induction of IL-β and tumor necrosis factor (TNF)-α has been shown in other systems, we investigated the possible interaction between these cytokines in regulating fibronectin production in CA SMC. First, we documented increased TNF-α expression in vivo in donor compared to host CA. Next, synthesis of fibronectin was measured in host and donor CA SMC following [35S]-methionine radiolabeling and gelatin-sepharose extraction. As previously shown with IL-β, increased donor CA SMC fibronectin synthesis was reduced to host levels in the presence of TNF-α antibodies, and exogenous TNF-α upregulated fibronectin synthesis in host CA SMC to levels in donor cells. In normal CA SMC, TNF-α-stimulated fibronectin production was downregulated to or below control levels in the presence of IL-β antibodies. Likewise, IL-β-stimulated fibronectin synthesis was downregulated to control levels when TNF-α neutralizing antibodies were added. Combining TNF-α and IL-β enhanced fibronectin production over that observed with either cytokine alone, but was not additive. Thus, our studies suggest that vascular SMC fibronectin synthesis is regulated by reciprocal induction of IL-β and TNF-α activity and provide the first demonstration of a ‘cytokine loop’ modulating matrix production.

This publication has 22 references indexed in Scilit: