RRC ID |
39898
|
著者 |
Haruta I, Kato Y, Hashimoto E, Minjares C, Kennedy S, Uto H, Yamauchi K, Kobayashi M, Yusa S, Müller U, Hayashi N, Miyazaki T.
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タイトル |
Association of AIM, a novel apoptosis inhibitory factor, with hepatitis via supporting macrophage survival and enhancing phagocytotic function of macrophages.
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ジャーナル |
J Biol Chem
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Abstract |
A hallmark of many inflammatory diseases is the destruction of tissue cells by infiltrating hematopoietic cells including lymphocytes, neutrophils, and macrophages. The regulation of apoptosis of both target tissue cells and the infiltrating cells is one of the key events that defines the initiation and the progression of inflammation. However, the precise picture of the apoptosis regulation of the cells at the inflammatory sites is still unclear. We recently isolated a novel apoptosis inhibitory factor, termed AIM, which is secreted exclusively by tissue macrophages. In this report, we present unique characteristics of AIM associated with liver inflammation (hepatitis), identified by introducing an experimental hepatitis in both AIM-transgenic mice, which overexpress AIM in the body, and normal mice. First, endogenous AIM expression in macrophages is rapidly increased in response to inflammatory stimuli. Second, AIM appears to inhibit the death of macrophages in the inflammatory regions, judging by the remarkably increased number of macrophages observed in the liver from transgenic mice. In addition, we show that AIM also enhances the phagocytosis by macrophages, which emphasizes the multifunctional character of AIM. All these findings strongly provoke an idea that AIM may play an important role in hepatitis pathogenesis in a sequential manner; first AIM expression is up-regulated by inflammatory stimuli, and then in an autocrine fashion, AIM supports the survival of infiltrating macrophages as well as enhances phagocytosis by macrophages, which may result in an efficient clearance of dead cells and infectious or toxic reagents.
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巻・号 |
276(25)
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ページ |
22910-4
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公開日 |
2001-6-22
|
DOI |
10.1074/jbc.M100324200
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PII |
S0021-9258(20)78585-6
|
PMID |
11294859
|
MeSH |
Animals
Apoptosis / physiology*
Cell Survival / physiology*
Hepatitis, Viral, Animal / metabolism*
Liver / pathology
Macrophages / cytology
Macrophages / immunology
Macrophages / metabolism*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phagocytosis / physiology*
Proteins / metabolism
Proteins / physiology*
Up-Regulation
|
IF |
4.238
|
引用数 |
41
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
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リソース情報 |
ヒト・動物細胞 |
|