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-1 in inflammation and the underlying mechanism. Human aortic endothelial cells were stimulated by ox-LDL (50 μg/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-1 receptor (IGF-1R) 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 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 inflammation by reducing HMGB1 release, suggesting an unexpected beneficial role of IGF-1 in inflammatory disease.
Department of Thoracic Surgery,  Yu Huang Ding Hospital, Yantai 264000,  China.
Xiaofeng
X
Yu
Chunyan
C
Xing
Yinghua
Y
Pan
Housheng
H
Ma
Jie
J
Zhang
Wenjun
W
Li
D001011:Aorta / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D018613:Microscopy, Confocal; D010084:Oxidation-Reduction; D010766:Phosphorylation / Q000187:drug effects; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D034622:RNA Interference; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D024243:HMGB1 Protein; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C415032:picropodophyllin; D018799:Intercellular Adhesion Molecule-1; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin