Background: Various cytokines and other compounds are produced in human adipose tissue and might have functions in the adipose tissue. They might be involved in complications associated with obesity and diabetes. Recently, interleukin-8 (IL-8) has been shown to be produced and released from human adipose tissue and/or adipocytes, suggesting IL-8 involvement in some obesity-related health complications. Therefore, we found it of interest to investigate whether IL-8 is involved in the insulin action in human adipocytes.
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.
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