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

Atherosclerosis, a multifactorial chronic inflammatory response, 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-I in inflammation and the underlying mechanism. Human aortic endothelial cells were stimulated by ox-LDL （50 ttg/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 immunosorbent assay. IGF-I receptor （IGF-IR） expression was assessed by reverse transcription-polymerase chain reaction and western blot analysis. IGF-1R phosphorylation was determined by western blot analysis. Ox-LDL stimulation reduced IGF-1R mRNA and protein expression but increased HMGBI release. IGF-1 treatment decreased ox- LDL-induced ICAM-1 expression potentially through reducing HMGB1 release, while picropodophyHin, an IGF- 1R specific inhibitor, increased the inflammatory response. in conclusion, IGF-1 can alleviate ox-LDL-induced inflammation by reducing HMGB1 release, suggesting an unexpected beneficial role of IGF-1 in inflammatory disease.