Angiotensin II enhances the increase in monocyte chemoattractant protein-1 production induced by tumor necrosis factor-α from 3T3-L1 preadipocytes

Abstract

Monocyte chemoattractant protein-1 (MCP-1) and angiotensin II (Ang II) in adipose tissue are thought to induce systemic insulin resistance in rodents; but the precise mechanism is not fully clarified. We examined the mechanism of Ang II-induced and/or tumor necrosis factor-a (TNF-a)-induced MCP-1 production from 3T3-L1 preadipocytes. The MCP-1 protein and MCP-1 mRNA expression in 3T3-L1 preadipocytes were increased significantly by stimulation with TNF-a. We found no significant increase in MCP-1 concentrations by Ang II alone; but it enhanced the TNF-a-induced MCP-1 mRNA expression in a dose-dependent manner. Then, we examined the effect of Ang II and/or TNF-a on phosphorylation of extracellular signal-regulated kinase (ERK), p38MAPK, and IkB-a. Ang II and TNF-a clearly enhanced ERK and p38MAPK phosphorylation. IkB-a phosphorylation was enhanced by TNF-a, but not by Ang II. The MCP-1 mRNA expression induced by TNF-a and co-stimulation with Ang II was inhibited by either ERK inhibitor, p38MAPK inhibitor or NF-kB inhibitor. Moreover, Ang II enhanced the activation of AP-1 (c-fos) induced by TNF-a. Our results suggest that Ang II may serve as an additional stimulus on the TNF-a-induced MCP-1 production through the ERKand p38MAPK-dependent pathways probably due to AP-1 activation.

Differential Effects of Grape Powder and Its Extract on Glucose Tolerance and Chronic Inflammation in High-Fat-Fed Obese Mice

“…It has been demonstrated that TNFα-induced MCP-1 gene expression in adipocytes or other cell types occurs via activation of the transcription factors NF-κB or AP-1 (i.e., c-Jun, c-fos, ATF), because the promoter of the MCP-1 gene contains NF-κB and AP-1 binding sites. 44,45 Indeed, we found that Q3G reduced TNFα-mediated phosphorylation of JNK and downstream c-Jun activation (Figure 4B), but not ERK activation or IκBα degradation (data not shown), in human primary adipocyte cultures. Further investigations examining upstream activators of TNFα-mediated inflammatory signaling are needed to understand how Q3G suppresses this pathway.…”

A Novel Role for Adipose Ephrin-B1 in Inflammatory Response

“…Importantly, various adipocytes-derived chemokines increase monocyte recruitment into adipose tissue and the MCP-1/CCR2 pathway is known to play a crucial role in monocyte/macrophage infiltration into obese adipose tissue [30-32], suggesting the involvement of adipose MCP-1 in the prevention of the metabolic syndrome. Inflammatory cytokines, such as TNF-α, interleukin-1β (IL-1β), and transforming growth factor-β (TGF-β), increase MCP-1 through the activation of ERK, nuclear factor-κB (NFκB), and c-Jun N-terminal kinase (JNK) pathway [33-35]. In the course of adipocyte hypertrophy, ERK is activated while mitogen-activated protein kinase phosphatase-1 (MKP-1) is inactivated [18].…”

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

“…Another important aspect of ANG II signaling in adipocytes is related to the adipocyte production of inflammatory mediators and chemoattractant that cause low-grade adipose tissue inflammation, and obesity and insulin resistance are closely associated with a state of low-grade inflammation in adipose tissues (394). Data demonstrate that ANG II enhances TNF-␣-induced MCP1 expression in 3T3-L1 preadipocytes via a ERK1/2-and p38MAPK-dependent pathways (37). An ARB with PPAR␥ receptor agonist activity, telmisartan, attenuated the release of the proinflammatory factors secreted from 3T3-L1 adipocytes and improved lipid metabolism possibly via activation of the MAPK pathway and upregulation of eNOS/NOS3 and carnitine palmitoyltransferase 1␣.…”