RRC ID 1463
著者 Suganami T, Nishida J, Ogawa Y.
タイトル A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha.
ジャーナル Arterioscler Thromb Vasc Biol
Abstract OBJECTIVE:Weight gain is associated with infiltration of fat by macrophages, suggesting that they are an important source of inflammation in obese adipose tissue. Here we developed an in vitro coculture system composed of adipocytes and macrophages and examined the molecular mechanism whereby these cells communicate.
METHODS AND RESULTS:Coculture of differentiated 3T3-L1 adipocytes and macrophage cell line RAW264 results in the marked upregulation of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), and the downregulation of the antiinflammatory cytokine adiponectin. Such inflammatory changes are induced by the coculture without direct contact, suggesting the role of soluble factors. A neutralizing antibody to TNF-alpha, which occurs mostly in macrophages, inhibits the inflammatory changes in 3T3-L1, suggesting that TNF-alpha is a major macrophage-derived mediator of inflammation in adipocytes. Conversely, free fatty acids (FFAs) may be important adipocyte-derived mediators of inflammation in macrophages, because the production of TNF-alpha in RAW264 is markedly increased by palmitate, a major FFA released from 3T3-L1. The inflammatory changes in the coculture are augmented by use of either hypertrophied 3T3-L1 or adipose stromal vascular fraction obtained from obese ob/ob mice.
CONCLUSIONS:We postulate that a paracrine loop involving FFAs and TNF-alpha between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue.
巻・号 25(10)
ページ 2062-8
公開日 2005-10-1
DOI 10.1161/01.ATV.0000183883.72263.13
PII 01.ATV.0000183883.72263.13
PMID 16123319
MeSH 3T3-L1 Cells Adipocytes / cytology Adipocytes / immunology* Adipocytes / metabolism Adipose Tissue / immunology Adipose Tissue / metabolism Adipose Tissue / pathology Animals Atherosclerosis / immunology Atherosclerosis / metabolism Atherosclerosis / pathology Cell Communication / immunology Chemokine CCL2 / genetics Chemokine CCL2 / metabolism Coculture Techniques Fatty Acids, Nonesterified / metabolism* Gene Expression Regulation / immunology Hypertrophy Inflammation / immunology Inflammation / metabolism Inflammation / pathology Macrophages / cytology Macrophages / immunology* Macrophages / metabolism Metabolic Syndrome / immunology* Metabolic Syndrome / metabolism* Metabolic Syndrome / pathology Mice Obesity / immunology Obesity / metabolism Obesity / pathology Paracrine Communication / immunology Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism*
IF 6.604
引用数 673
WOS 分野 PERIPHERAL VASCULAR DISEASE HEMATOLOGY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)