Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis.
Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis.
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DOI：
10.1371/journal.pone.0021381
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Tacke F
中科院分区：
文献类型：
--
作者：
Zimmermann HW;Seidler S;Gassler N;Nattermann J;Luedde T;Trautwein C;Tacke F
白介素8(IL-8，CXCL8)是一种对中性粒细胞有很强趋化作用的化学物质，在急性肝脏炎症中起重要作用。关于IL-8在慢性肝病(CLD)中的作用知之甚少，但有报道称，与酒精和丙型肝炎相关的CLD中IL-8水平升高。我们研究了CLD患者IL-8及其受体CXCR1和CXCR2的调节，以及可能的IL-8反应细胞。测定慢性阻塞性肺病患者(n = 2 0 0)和健康对照组(n = 14 1)血清IL-8水平。取肝组织标本(n = 41)进行IL-8、CXCR1和CXCR2基因表达定量，并进行中性粒细胞和巨噬细胞免疫组织化学染色。分析患者(n = )和对照组(n = 31)纯化的单核细胞CXCR1和CXCR2的表达。体外分析研究了不同白细胞亚群分泌IL-8的情况。慢性肝病患者血清IL-8水平明显升高，以终末期肝硬变患者更为明显。有趣的是，胆汁淤积性疾病患者的血清IL-8浓度最高。IL-8与肝功能、炎性细胞因子、非侵袭性纤维化标志物相关。肝内IL-8和CXCR1表达明显上调。然而，肝内IL-8仅与原发性胆汁性肝硬变(PBC)患者的中性粒细胞浸润有关。在非淤胆型肝硬变中，IL-8和CXCR1水平升高与肝巨噬细胞聚集有关。肝硬变患者外周血单核细胞上CXCR1表达增加，而CXCR2或CXCR3表达增加。此外，CLD患者的单核细胞来源的巨噬细胞，特别是非经典的CD16+亚型，在体外显示出增强的IL-8分泌。IL-8在慢性肝病中被强烈激活，因此可能在肝脏炎症中起作用。我们的研究表明，IL-8通过CXCR1在人肝硬变中对肝巨噬细胞的募集和激活具有新的作用。
Interleukin-8 (IL-8, CXCL8) is a potent chemoattractant for neutrophils and contributes to acute liver inflammation. Much less is known about IL-8 in chronic liver diseases (CLD), but elevated levels were reported from alcoholic and hepatitis C-related CLD. We investigated the regulation of IL-8, its receptors CXCR1 and CXCR2 and possible IL-8 responding cells in CLD patients. Serum IL-8 levels were measured in CLD patients (n = 200) and healthy controls (n = 141). Intrahepatic IL-8, CXCR1 and CXCR2 gene expression was quantified from liver samples (n = 41), alongside immunohistochemical neutrophil (MPO) and macrophage (CD68) stainings. CXCR1 and CXCR2 expression was analyzed on purified monocytes from patients (n = 111) and controls (n = 31). In vitro analyses explored IL-8 secretion by different leukocyte subsets. IL-8 serum levels were significantly increased in CLD patients, especially in end-stage cirrhosis. Interestingly, patients with cholestatic diseases exhibited highest IL-8 serum concentrations. IL-8 correlated with liver function, inflammatory cytokines and non-invasive fibrosis markers. Intrahepatically, IL-8 and CXCR1 expression were strongly up-regulated. However, intrahepatic IL-8 could only be associated to neutrophil infiltration in patients with primary biliary cirrhosis (PBC). In non-cholestatic cirrhosis, increased IL-8 and CXCR1 levels were associated with hepatic macrophage accumulation. In line, CXCR1, but not CXCR2 or CXCR3, expression was increased on circulating monocytes from cirrhotic patients. Moreover, monocyte-derived macrophages from CLD patients, especially the non-classical CD16+ subtype, displayed enhanced IL-8 secretion in vitro. IL-8 is strongly activated in CLD, thus likely contributing to hepatic inflammation. Our study suggests a novel role of IL-8 for recruitment and activation of hepatic macrophages via CXCR1 in human liver cirrhosis.
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影响因子：
20.3
作者：
Emadi, S;Clay, D;Le Bousse-Kerdilès, MC
通讯作者：
Le Bousse-Kerdilès, MC
影响因子：
2.3
作者：
Jaeschke, H
通讯作者：
Jaeschke, H
影响因子：
3.1
作者：
Kobayashi, Yoshiro
通讯作者：
Kobayashi, Yoshiro
DOI：
10.1046/j.1440-1746.2000.02232.x
发表时间：
2000-11-01
影响因子：
4.1
作者：
Kirsch, R;Woodburne, VE;Kirsch, RE
通讯作者：
Kirsch, RE
影响因子：
5.5
作者：
MOROHASHI, H;MIYAWAKI, T;MUKAIDA, N
通讯作者：
MUKAIDA, N