Chemokine production by human vascular smooth muscle cells: modulation by IL-13

1 The production of chemokines by vascular smooth muscle cells (SMC) is implicated in the pathogenesis of atherosclerosis, although the factors regulating chemokine production by these cells are incompletely characterized. 2 We describe the differential stimulation of interleukin-(IL)-8, monocyte chemoattractant protein (MCP)-1 and regulated on activation normal T-cell expressed and secreted (RANTES) synthesis following treatment of human vascular SMC with IL-1 alpha or tumour necrosis factor alpha (TNF alpha). Under basal conditions, cultured SMC release very low amounts of IL-8, MCP-1 and RANTES as assessed by specific ELISA. Concentration-response studies with IL-1 alpha or TNF alpha revealed that each stimulus induced a similar amount of MCP-1. In contrast approximately three fold more IL-8 was induced by IL-1 alpha than by TNF alpha whereas significant RANTES production was induced only by TNF alpha. These findings point to a divergence in the regulation of synthesis of the different chemokines in response to IL-1 alpha or TNF alpha stimulation. 3 The T-cell derived cytokines IL-10 and IL-13 were also found to have differential effects on chemokine production by SMC. IL-13, but not IL-IO, significantly enhanced IL-8 and MCP-1 release in response to IL-1 alpha or TNF alpha. This increase in chemokine release appeared to be accounted for by increased mRNA expression. 4 These findings provide support for the concept that smooth muscle cells can have an active role in a local immune response via the production of chemokines which can be selectively modulated by T-cell derived cytokines.