Angiotensin II enhances the increase in monocyte chemoattractant protein-1 production induced by tumor necrosis factor-{alpha} from 3T3-L1 preadipocytes.
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-alpha (TNF-alpha)-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-alpha. We found no significant increase in MCP-1 concentrations by Ang II alone; but it enhanced the TNF-alpha-induced MCP-1 mRNA expression in a dose-dependent manner. Then, we examined the effect of Ang II and/or TNF-alpha on phosphorylation of extracellular signal-regulated kinase (ERK), p38MAPK, and IkappaB-alpha. Ang II and TNF-alpha clearly enhanced ERK and p38MAPK phosphorylation. IkappaB-alpha phosphorylation was enhanced by TNF-alpha, but not by Ang II. The MCP-1 mRNA expression induced by TNF-alpha and co-stimulation with Ang II was inhibited by either ERK inhibitor, p38MAPK inhibitor or NF-kappaB inhibitor. Moreover, Ang II enhanced the activation of AP-1 (c-fos) induced by TNF-alpha. Our results suggest that Ang II may serve as an additional stimulus on the TNF-alpha-induced MCP-1 production through the ERK-and p38MAPK-dependent pathways probably due to AP-1 activation.
1st Department of Medicine, Toyama University, Sugitani 2630, Toyama-shi 930-0194, Japan.
Sachie
S
Asamizu
Masaharu
M
Urakaze
Chikaaki
C
Kobashi
Manabu
M
Ishiki
Amal Khalifa
AK
Norel Din
Shiho
S
Fujisaka
Yukiko
Y
Kanatani
Agussalim
A
Bukahari
Satoko
S
Senda
Hikari
H
Suzuki
Yuh
Y
Yamazaki
Minoru
M
Iwata
Isao
I
Usui
Katsuya
K
Yamazaki
Hirofumi
H
Ogawa
Hiroshi
H
Ogawa
Masashi
M
Kobayashi
Kazuyuki
K
Tobe
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018932:Chemokine CCL2; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases