MAPK/p38 regulation of cytoskeleton rearrangement accelerates induction of macrophage activation by TLR4, but not TLR3

Abstract

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 α- and β-tubulin was markedly decreased following LPS stimulation. By contrast, α- and β-tubulin expression were only mildly increased following poly(I:C) treatment. However, the expression of β-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.

The E3 ubiquitin ligase MuRF2 attenuates LPS‐induced macrophage activation by inhibiting production of inflammatory cytokines and migration

“…Male C57BL/6J mice, 6–8 weeks old, were obtained from the Animal Research Committee of the Institute of Biology and Cell Biology (Shanghai, China) and housed in a specific environment as previously described . All animal experiments were undertaken in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals , with the approval of the Scientific Investigation Board of the Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China.…”

Role of inflammatory response in liver diseases: Therapeutic strategies

“…The Kupffer cells of the liver are the first to be attacked by the damage produced, and express TLR4 to which lipopolysaccharides (LPS) bind. This produces the activation of NF-kB, mitogen-activated protein kinase (MAPK)[ 21 ] extracellular signal-regulated kinase-1 (ERK1), p38, c-jun N-terminal kinase (JNK) and interferon regulatory factor 3(IRF3)[ 22 ], which finally triggers the production of proinflammatory cytokines and enhances IFN-β and STAT1 expression[ 23 ]. The proinflammatory stimulus facilitates hepatocyte damage, contributing to the secretion of profibrogenic cytokines such as transforming growth factor beta (TGF-β) and the platelet-derived growth factor (PDGF), promoting the activation of HSCs.…”

Negative feedback loop of ERK/CREB/miR‐212‐3p inhibits HBeAg‐induced macrophage activation

“…Previous studies demonstrated that LPS stimulation could activate MAPK signalling and lead to production of cytokines, including IL-6 and TNF-α in macrophages. 19 To explore the role of MAPK in macrophage activation induced by HBeAg, we performed Western blot experiment to detect the expression of non-phosphorylation and phosphorylation of MAPK in RAW264.7 cells treated with HBeAg. As can be seen in Figure 3A, the phosphorylated levels of key proteins in MAPK signal pathway, including ERK, JNK and p38, were all elevated after treatment with HBeAg and reached their peak at 30 minutes, and then began to decrease gradually at 60 minutes.…”