Original Article IGF-1 alleviates ox-LDL-induced inflammation via reducing HMGB1 release in

Atherosclerosis, a multifactorial chronic inflammatory re-sponse, is closely associated with oxidatively modified low-density lipoprotein (ox-LDL). High-mobility group box 1 (HMGB1) is a DNA-binding protein, which upon release from cells exhibits potent inflammatory action. Insulin-like growth factor 1 (IGF-1) can elicit a repertoire of cellular responses including proliferation and anti-apoptosis. However, the role of IGF-1 in inflammation is still unclear. In the present study, we aimed to investigate the role of IGF-1 in inflammation and the underlying mechanism. Human aortic endothelial cells were stimulated by ox-LDL (50 mg/ml) to induce inflammation. The expression of intercellular adhesion molecule 1 (ICAM-1) was assessed by western blot analysis and immunofluorescence. The release of HMGB1 was determined by enzyme-linked im-munosorbent assay. IGF-1 receptor (IGF-1R) expression was assessed by reverse transcription-polymerase chain re-action and western blot analysis. IGF-1R phosphorylation was determined by western blot analysis. Ox-LDL stimula-tion reduced IGF-1R mRNA and protein expression but increased HMGB1 release. IGF-1 treatment decreased ox-LDL-induced ICAM-1 expression potentially through reducing HMGB1 release, while picropodophyllin, an IGF-1R specific inhibitor, increased the inflammatory response. In conclusion, IGF-1 can alleviate ox-LDL-induced inflam-mation by reducing HMGB1 release, suggesting an unex-pected beneficial role of IGF-1 in inflammatory disease. Keywords inflammation; insulin-like growth factor 1; high-mobility group box 1; human aortic endothelial cell