Cross-talk between angiotensin-II and toll-like receptor 4 triggers a synergetic inflammatory response in rat mesangial cells under high glucose conditions.
Toll-like Receptor 4 (TLR4) may play an important role in the pathogenesis of diabetic nephropathy (DN). In this study, We observed the TLR4 signal and the release of inflammation factors after angiotensin II (Ang II) stimulation in rat mesangial cells (MCs) under high glucose conditions, this revealed the innate immune mechanism of injury by Ang II in DN. Our data showed that TLR4 and MyD88 were up-regulated significantly in high glucose and AngII-induced MCs; meanwhile, NF-κB as well as MCP-1, IL-6 were also highly expressed. In cells that were transfected with TLR4 SiRNA，the parameters were greatly inhibited; similar effects were detected in cells that were treated with Irbesartan. We concluded that Ang II synergized with high glucose in the release of pro-inflammatory factors mainly through the upregulation of TLR4 signaling in MCs, Cross-talk between Ang II and TLR4 contributed to the MC inflammatory injury under high glucose conditions.
Division of Nephrology, The First Affiliated Hospital of NanChang University, China. Electronic address: lvjinlei97@163.com.
Jinlei
J
Lv
Division of Nephrology and Organ Transplatation, The First Affiliated Hospital of NanChang University, China.
Qinkai
Q
Chen
Division of Ophthalmology, The First Affiliated Hospital of NanChang University, China.
Yi
Y
Shao
Division of Nephrology, The First Affiliated Hospital of NanChang University, China.
Yuhua
Y
Chen
Division of Nephrology and Organ Transplatation, The First Affiliated Hospital of NanChang University, China. Electronic address: sj88692702@163.com.
Jun
J
Shi
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D050527:Mesangial Cells / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012084:Renin-Angiotensin System; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D015850:Interleukin-6; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D000804:Angiotensin II; D005947:Glucose
Angiotensin II; High glucose; Inflammation; Mesangial cell; Toll like receptor 4