Contrast Media-Induced Renal Inflammation Is Mediated Through HMGB1 and Its Receptors in Human Tubular Cells.
With the rapid development of imaging diagnosis and interventional therapy, contrast media (CM) are widely used in clinics. However, contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure accounting for 10-12% of all causes of hospital-acquired renal failure. Recent study found that inflammation may participate in the pathogenesis of CIN, but the role of it remains unclear. HK-2 cells were treated with Iohexol, Urografin, and mannitol. Two types of CM increased the release of HMGB1 in cell supernatant accompanied by increased expression of TLR2 and CXCR4. Iohexol and Urografin also caused a significant increase in NF-κB followed by the release of IL-6 and MCP-1. To clarify the role of HMGB1, TLR2, and CXCR4, glycyrrhizin, anti-TLR2-IgG, and AMD3100 were used to inhibit HMGB1, TLR2, and CXCR4, respectively. Significant decrease in the expression of TLR2, CXCR4, nuclear NF-κB, and the release of IL-6 and MCP-1 were observed. These results indicate that TLR2 and CXCR4 signaling are involved in CM-induced HK-2 cell injury model in an HMGB1-dependent pathway, which may provide a new target for the prevention and the treatment of CIN.
Clinical Pharmacy and Pharmacology Research Institute, The Third Xiangya Hospital of Central South University , Changsha, People's Republic of China .
Xiao-Feng
XF
Guan
Clinical Pharmacy and Pharmacology Research Institute, The Third Xiangya Hospital of Central South University , Changsha, People's Republic of China .
Qing-Jie
QJ
Chen
Clinical Pharmacy and Pharmacology Research Institute, The Third Xiangya Hospital of Central South University , Changsha, People's Republic of China .
Xiao-Cong
XC
Zuo
Clinical Pharmacy and Pharmacology Research Institute, The Third Xiangya Hospital of Central South University , Changsha, People's Republic of China .
Ren
R
Guo
Clinical Pharmacy and Pharmacology Research Institute, The Third Xiangya Hospital of Central South University , Changsha, People's Republic of China .
Xiang-Dong
XD
Peng
Clinical Pharmacy and Pharmacology Research Institute, The Third Xiangya Hospital of Central South University , Changsha, People's Republic of China .
Jiang-Lin
JL
Wang
Clinical Pharmacy and Pharmacology Research Institute, The Third Xiangya Hospital of Central South University , Changsha, People's Republic of China .
Wen-Jun
WJ
Yin
Clinical Pharmacy and Pharmacology Research Institute, The Third Xiangya Hospital of Central South University , Changsha, People's Republic of China .
Dai-Yang
DY
Li
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D003287:Contrast Media / Q000494:pharmacology*; D003974:Diatrizoate Meglumine / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
C111835:CCL2 protein, human; C527276:CXCR4 protein, human; D018932:Chemokine CCL2; D003287:Contrast Media; D024243:HMGB1 Protein; D015850:Interleukin-6; D019718:Receptors, CXCR4; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051996:Transcription Factor RelA; D003974:Diatrizoate Meglumine; D019695:Glycyrrhizic Acid
CXCR4; HMGB1; TLR2; contrast media; inflammation