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.