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Effect of Kupffer cell blockade on activation of mitogen-activated protein kinases in response to lipopolysaccharide
Authors:CHEN Hong-mei  XU Rui-ling  ZHANG Lei  ZHENG Tian-zhen  LI Wei
Institution:1.Department of Physiology,Medical College,3 Department of General Surgery,The First Hospital,Lanzhou University,Lanzhou 730000,China;2.Department of Pathophysiology,Shanxi Medical University,Taiyuan 030001,China.E-mail: qifan_0530@163.com
Abstract:AIM: Using the mouse model of lipopolysaccharide(LPS) attack,we study the effect of Kupffer cell (KC) blockade on the activation of mitogen-activated protein kinases(MAPKs) signal transduction pathway induced by LPS.METHODS: GdCl3 (10 mg/kg) or the same volume of NS was continually injected intravenously at 48 h and 24 h before LPS (5 mg/kg) was injected into the male mice of Kunming species.The liver was then took out and KCs were isolated 30 minute after LPS was injected.The KCs isolated from the mice were cultured,and pretreated with GdCl3 (100 μmol/L) for 1 h.The culture medium containing LPS (100 μg/L) was added and continuously incubated for 30 minute.The protein expression and phosphorylation level of ERK1/2 and p38MAPK in liver or KCs were assayed in vivo and in vitro,and effect of GdCl3 on the phagocytosis function was observed,respectively.RESULTS: LPS induced the protein phosphorylation of ERK1/2 and p38MAPK in KCs or liver,no effect on the protein expression was observed.GdCl3 treatment inhibited LPS-induced KCs activation and secretion of TNF-α,however,it had no effect on ERK1/2 and p38MAPK in KCs or liver,neither at the protein expression nor the phosphorylation.KCs secreted a few TNF-α with short time treatment with GdCl3 alone in vitro.CONCLUSION: KC blockade with GdCl3 alleviates LPS-induced KCs activation and the release of TNF-α not through modulating intracellular ERK1/2 or p38MAPK signal transduction pathways.We presume that GdCl3 might reduce liver injury through cross talk of other intracellular signal transduction pathways (JNK,NF-кB,GPCR,etc).
Keywords:Kupffer cells  Lipopolysaccharide  Gadolinium chlorides  Mitogen-activated protein kinases  Tumor necrosis factor  
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