The anti-inflammatory effects of adiponectin are mediated via a heme oxygenase-1-dependent pathway in rat Kupffer cells.
The anti-inflammatory effects of adiponectin are mediated via a heme oxygenase-1-dependent pathway in rat Kupffer cells.
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DOI：
10.1002/hep.23427
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发表时间：
2010-04
期刊：
影响因子：
13.5
通讯作者：
Nagy, Laura E.
中科院分区：
文献类型：
--
作者：
Mandal, Palash;Park, Pil-Hoon;McMullen, Megan R.;Pratt, Brian T.;Nagy, Laura E.
免疫调节细胞因子的表达和活性改变在酒精性肝病的发病机制中起主要作用。慢性乙醇喂养增加了枯否细胞（肝巨噬细胞）对脂多糖（LPS）的敏感性，导致肿瘤坏死因子-α（TNF-α）表达增加。通过用脂联素（一种抗炎脂肪因子）处理枯否细胞的原代培养物，使这种致敏作用正常化。在这里，我们测试的假设，脂联素介导的抑制LPS信号在库普弗细胞介导的白细胞介素-10（IL-10）/血红素加氧酶-1（HO-1）途径后，慢性乙醇喂养。在Kupffer细胞原代培养物中用siRNA敲低IL-10表达可阻止球状脂联素（gAcrp）对LPS刺激的TNF-α表达的抑制作用。gAcrp增加IL-10 mRNA和蛋白表达，以及IL-10诱导基因HO-1的表达;与成对喂养对照组相比，乙醇喂养大鼠的枯否细胞中的表达更高。虽然库普弗细胞上的IL-10受体表面表达不受乙醇喂养的影响，但乙醇喂养后库普弗细胞中IL-10介导的STAT 3磷酸化和HO-1表达更高。通过HO-1抑制剂锌原卟啉处理或通过siRNA敲低HO-1抑制HO-1活性，可阻止gAcrp对Kupffer细胞中LPS刺激的TNF-α表达的抑制作用。慢性乙醇暴露后，LPS刺激的小鼠肝脏TNF-α表达增加。当用钴原卟啉处理小鼠以诱导HO-1表达时，乙醇诱导的对LPS的敏感性得到改善。gAcrp通过激活IL-10/STAT 3/HO-1途径阻止库普弗细胞中LPS刺激的TNF-α表达。来自乙醇喂养大鼠的枯否细胞对gAcrp的抗炎作用高度敏感;这种敏感性与IL-10的表达增加和敏感性相关。
Altered expression and activity of immunomodulatory cytokines plays a major role in the pathogenesis of alcoholic liver disease. Chronic ethanol feeding increases the sensitivity of Kupffer cells, the resident hepatic macrophage, to lipopolysaccharide (LPS), leading to increased tumor necrosis factor-α (TNF-α) expression. This sensitization is normalized by treatment of primary cultures of Kupffer cells with adiponectin, an anti-inflammatory adipokine. Here we tested the hypothesis that adiponectin-mediated suppression of LPS signaling in Kupffer cells is mediated via an interleukin-10 (IL-10)/heme oxygenase-1 (HO-1) pathway after chronic ethanol feeding. Knock-down of IL-10 expression in primary cultures of Kupffer cells with siRNA prevented the inhibitory effect of globular adiponectin (gAcrp) on LPS-stimulated TNF-α expression. gAcrp increased IL-10 mRNA and protein expression, as well as expression of the IL-10 inducible gene, HO-1; expression was higher in Kupffer cells from ethanol-fed rats compared to pair-fed controls. While IL-10 receptor surface expression on Kupffer cells was not affected by ethanol feeding, IL-10-mediated phosphorylation of STAT3 and expression of HO-1 was higher in Kupffer cells after ethanol feeding. Inhibition of HO-1 activity, either by treatment with the HO-1 inhibitor, zinc protoporphyrin, or by siRNA knock-down of HO-1, prevented the inhibitory effect of gAcrp on LPS-stimulated TNF-α expression in Kupffer cells. LPS-stimulated TNF-α expression in liver was increased in mice after chronic ethanol exposure. When mice were treated with cobalt protoporphyrin to induce HO-1 expression, ethanol-induced sensitivity to LPS was ameliorated. gAcrp prevents LPS-stimulated TNF-α expression in Kupffer cells via the activation of the IL-10/STAT3/HO-1 pathway. Kupffer cells from ethanol-fed rats are highly sensitive to the anti-inflammatory effects of gAcrp; this sensitivity is associated with both increased expression and sensitivity to IL-10.
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DOI：
10.1016/j.bbrc.2004.02.130
发表时间：
2004-04-09
影响因子：
3.1
作者：
Wulster-Radcliffe, MC;Ajuwon, KM;Spurlock, ME
通讯作者：
Spurlock, ME
DOI：
10.1124/jpet.107.135285
发表时间：
2008-06-01
影响因子：
3.5
作者：
Kim, Dong Hyun;Burgess, Angela P.;Abraham, Nader G.
通讯作者：
Abraham, Nader G.
影响因子：
4.8
作者：
Park, Pil-hoon;McMullen, Megan R.;Nagy, Laura E.
通讯作者：
Nagy, Laura E.
DOI：
10.1111/j.1530-0277.2006.00012.x
发表时间：
2006-01-01
影响因子：
3.2
作者：
Mandrekar, P;Catalano, D;Szabo, G
通讯作者：
Szabo, G
影响因子：
4.8
作者：
MAINES, MD
通讯作者：
MAINES, MD