Effects of advanced glycation end products on the secretion of proinflammatory chemokines in vascular smooth muscle cells

Abstract

To investigate the effects of advanced glycation end products (AGEs) on the secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in vascular smooth muscle cells (VSMCs) and explore its possible intracellular signaling mechanism. Primary rat VSMCs were isolated and identified. VSMCs were treated with glycation serum albumin (GSA), an important component of AGEs, in series of concentrations and time. The role of MAPK and NF-κB inhibitors was confirmed. The levels of MCP-1 and IL-8 were determined by enzyme-linked immunosorbent assay (ELISA). VSMCs were treated with GSA at the doses of 10 µg/ml, 100 µg/ml and 500 µg/ml respectively. In comparison with the control group, the levels of MCP-1 (13.01 ng/ml ± 0.12 ng/ml vs 7.02 ng/ml ± 0.26 ng/ml, P < 0.05) and IL-8 (12.6 ng/ml ± 0.86 ng/ml vs 3.07 ng/ml ± 0.35 ng/ml, P < 0.05) increased in the GSA-treated group, especially at the concentration of 100 µg/ml. After adjustment for cells proliferation, the levels of MCP-1 and IL-8 were still higher in the GSA-treated group. After a pretreatment of PDTC (10 µmol/L), SB203580 (5 µmol/L) and MG132 (10 µmol/L), the levels of MCP-1 and IL-8 decreased. However, it had no change when pretreated with PD98059 (20 µmol/L). GSA promotes the secretion of MCP-1 and IL-8 in VSMCs. Such an effect is not dependent on cellular proliferation. It may be realized through an activation of NF-κB by p38MAPK-sensitive intracellular signaling pathway.