Endogenous interleukin-1α promotes a proliferative and proinflammatory phenotype in human vascular smooth muscle cells

During vascular disease and following injury, vascular smooth muscle cells (VSMC) proliferate and produce inflammation-promoting cytokines and chemokines. Similar phenotypic changes can be elicited in vitro by activation of Toll-like receptors (TLR) within VSMC. TLR-activated VSMC also produce IL-1α, but it is unknown whether endogenous IL-1α stimulates VSMC in an autocrine manner. Here we tested the hypothesis that endogenous IL-1α contributes to TLR-induced proliferation and chemokine release in human VSMC by using RNA interference to knock down IL-1α expression. Knockdown of IL-1α abolished TLR-induced proliferation and suppressed TLR4-induced release of monocyte chemoattractant protein-1 (MCP-1) by VSMC, indicating that endogenous IL-1α plays a crucial role in both responses. Serum, PDGF, FGF-2, and EGF each increased cellular IL-1α concentrations, and IL-1α knockdown inhibited serum- and PDGF-induced DNA synthesis, further indicating that endogenous IL-1α also contributed to VSMC responses to growth ...