MAPK/p38 regulation of cytoskeleton rearrangement accelerates induction of macrophage activation by TLR4, but not TLR3
作者
Bian, HJ;Li, FF;Wang, WW;Zhao, Q;Gao, SS;Ma, JC;Li, X;Ren, WH;Qin, CY;Qi, JN
作者单位
[Bian, Hongjun] Shandong Univ, Shandong Prov Hosp, Dept Emergency Med, Jinan 250021, Shandong, Peoples R China.;-;[Li, Feifei; Wang, Wenwen; Zhao, Qi; Gao, Shanshan; Ma, Jincai; Li, Xiao; Ren, Wanhua; Qin, Chengyong] Shandong Univ, Shandong Prov Hosp, Dept Gastroenterol, Jinan 250021, Shandong, Peoples R China.;-;[Ma, Jincai] Jinan Fifth Peoples Hosp, Dept Gastroenterol, Jinan 250022, Shandong, Peoples R China.;-;[Qi, Jianni] Shandong Univ, Shandong Prov Hosp, Cent Lab, 324 Jingwu Rd, Jinan 250021, Shandong, Peoples R China.
摘要
Toll-like receptor 3 (TLR3) and TLR4 utilize adaptor proteins to activate mitogen-activated protein kinase (MAPK), resulting in the acute but transient inflammatory response aimed at the clearance of pathogens. In the present study, it was demonstrated that macrophage activation by lipopolysaccharide (LPS) or poly(I:C), leading to changes in cell morphology, differed significantly between the mouse macrophage cell line RAW264.7 and mouse primary peritoneal macrophages. Moreover, the expression of alpha- and beta-tubulin was markedly decreased following LPS stimulation. By contrast, alpha- and beta-tubulin expression were only mildly increased following poly(I:C) treatment. However, the expression of beta-actin and GAPDH was not significantly affected. Furthermore, it was verified that vincristine pretreatment abrogated the cytoskeleton rearrangement and decreased the synthesis and secretion of proinflammatory cytokines and migration of macrophages caused by LPS. Finally, it was observed that the MAPK/p38 signaling pathway regulating cytoskeleton rearrangement may participate in LPS-induced macrophage cytokine production and migration. Overall, the findings of the present study indicated that MAPK/p38 regulation of the cytoskeleton, particularly tubulin proteins, plays an important role in LPS-induced inflammatory responses via alleviating the synthesis and secretion of proinflammatory cytokines and inhibiting the migration of macrophages.
关键词
IFN-BETA PRODUCTION; ACTIN CYTOSKELETON; IN-VIVO; CELLS; REORGANIZATION; RECOGNITION; VINCRISTINE; INHIBITION; ENDOTOXIN; LEUKEMIA