論文 - 詳細
| RRC ID | 42806 |
|---|---|
| 著者 | Suganami T, Tanimoto-Koyama K, Nishida J, Itoh M, Yuan X, Mizuarai S, Kotani H, Yamaoka S, Miyake K, Aoe S, Kamei Y, Ogawa Y. |
| タイトル | Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. |
| ジャーナル | Arterioscler Thromb Vasc Biol |
| Abstract |
OBJECTIVE:Previous studies demonstrated that obese adipose tissue is characterized by increased infiltration of macrophages, suggesting that they might represent an important source of inflammation. Using an in vitro coculture system composed of 3T3-L1 adipocytes and RAW264 macrophages, we previously demonstrated that saturated fatty acids (FAs) and tumor necrosis factor (TNF)-alpha derived from adipocytes and macrophages, respectively, play a major role in the coculture-induced inflammatory changes. METHODS AND RESULTS:Coculture of adipocytes and macrophages resulted in the activation of nuclear factor-kappaB (NF-kappaB), a primary regulator of inflammatory responses, in both cell types. Pharmacological inhibition of NF-kappaB markedly suppressed the coculture-induced production of proinflammatory cytokines and adipocyte lipolysis. Peritoneal macrophages obtained from Toll-like receptor 4 (TLR4) mutant mice exhibited marked attenuation of TNFalpha production in response to saturated FAs. Notably, coculture of hypertrophied adipocytes and TLR4-mutant macrophages resulted in marked inhibition of proinflammatory cytokine production and adipocyte lipolysis. We also observed that endogenous FAs, which are released from adipocytes via the beta3-adrenergic stimulation, resulted in the activation of the TLR4/NF-kappaB pathway. CONCLUSIONS:These findings suggest that saturated FAs, which are released in large quantities from hypertrophied adipocytes via the macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for TLR4, thereby inducing the inflammatory changes in both adipocytes and macrophages through NF-kappaB activation. |
| 巻・号 | 27(1) |
| ページ | 84-91 |
| 公開日 | 2007-1-1 |
| DOI | 10.1161/01.ATV.0000251608.09329.9a |
| PII | 01.ATV.0000251608.09329.9a |
| PMID | 17082484 |
| MeSH | Adipocytes / drug effects Adipocytes / pathology* Animals Cell Communication / drug effects* Cell Line Coculture Techniques Fatty Acids / pharmacology* Fatty Acids, Nonesterified / metabolism Gene Expression Regulation / physiology Hypertrophy / pathology Inflammation / pathology Lipolysis Macrophages / drug effects Macrophages / pathology* Mice Mice, Mutant Strains NF-kappa B / genetics NF-kappa B / physiology* Obesity / metabolism Obesity / pathology Obesity / physiopathology Signal Transduction / genetics Signal Transduction / physiology* Toll-Like Receptor 4 / genetics Toll-Like Receptor 4 / physiology* Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism |
| IF | 6.604 |
| 引用数 | 506 |
| WOS 分野 | HEMATOLOGY PERIPHERAL VASCULAR DISEASE |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |