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慢性丙型肝炎患者白细胞介素-8和hIRH(基质细胞衍生因子1α/前B细胞生长刺激因子)mRNA表达及组织学活性指数

Interleukin-8 and hIRH (SDF1-alpha/PBSF) mRNA expression and histological activity index in patients with chronic hepatitis C.

作者信息

Shimoda K, Begum N A, Shibuta K, Mori M, Bonkovsky H L, Banner B F, Barnard G F

机构信息

Department of Medicine, University of Massachusetts Medical Center, Worcester 01655-0310, USA.

出版信息

Hepatology. 1998 Jul;28(1):108-15. doi: 10.1002/hep.510280116.

Abstract

Recombinant human intercrine reduced in hepatomas (hIRH)/stromal cell-derived factor 1 (SDF1-alpha)/pre-B-cell growth-stimulating factor (PBSF), a new chemokine, exhibits an in vitro chemotaxis to neutrophils and a mixed in vivo chemotactic activity to neutrophils, lymphocytes, and monocytes in a rat intradermal injection model. We have investigated the messenger RNA (mRNA) expression of interleukin-8 (IL-8) and hIRH, in chronic hepatitis C of differing severity. Levels of expression of IL-8 and hIRH mRNA obtained from 37 human liver biopsy samples were measured by reverse-transcription and semiquantitative polymerase chain reaction (RT-PCR) amplification. We examined the correlation between mRNA expression and components of the histological activity index (HAI). Patients with HAI > or = 8 had a significantly higher corrected IL-8 mRNA expression ratio (0.24 +/- 0.13 [mean +/- SD]; n = 20) than those with HAI < or = 7 (0.05 < or = 0.03; n = 17; P < .0001). Additionally, IL-8 mRNA expression was strongly associated with the severity of portal inflammation (PI) (high PI vs. low PI, 0.22 +/- 0.14 vs. 0.05 +/- 0.04; P < .0001) and with the presence of bile duct lesions (0.29 +/- 0.15 vs. 0.11 +/- 0.1; P < .01). In contrast, hIRH mRNA expression was not associated with the total HAI, any components of the HAI, or bile duct inflammation or injury. These results suggest that hIRH, although having the -CXC-, alpha chemokine motif, and exhibiting in vivo and in vitro inflammatory activity as does IL-8, plays a different role from IL-8 in hepatic inflammation and injury. IL-8 expression is directly associated with inflammation in patients with chronic hepatitis C, while hIRH expression does not correlate with histopathological severity of inflammation.

摘要

重组人肝癌中减少的内分泌因子(hIRH)/基质细胞衍生因子1(SDF1-α)/前B细胞生长刺激因子(PBSF),一种新的趋化因子,在大鼠皮内注射模型中对中性粒细胞表现出体外趋化性,对中性粒细胞、淋巴细胞和单核细胞表现出混合的体内趋化活性。我们研究了不同严重程度的慢性丙型肝炎中白细胞介素-8(IL-8)和hIRH的信使核糖核酸(mRNA)表达。通过逆转录和半定量聚合酶链反应(RT-PCR)扩增,测量了从37例人类肝活检样本中获得的IL-8和hIRH mRNA的表达水平。我们检查了mRNA表达与组织学活动指数(HAI)各成分之间的相关性。HAI≥8的患者校正后的IL-8 mRNA表达率(0.24±0.13[平均值±标准差];n = 20)显著高于HAI≤7的患者(0.05±0.03;n = 17;P <.0001)。此外,IL-8 mRNA表达与门静脉炎症(PI)的严重程度密切相关(高PI与低PI,0.22±0.14对0.05±0.04;P <.0001),也与胆管病变的存在相关(0.29±0.15对0.11±0.1;P <.01)。相比之下,hIRH mRNA表达与总HAI、HAI的任何成分、胆管炎症或损伤均无关。这些结果表明,hIRH虽然具有-CXC-、α趋化因子基序,并且与IL-8一样在体内和体外表现出炎症活性,但在肝脏炎症和损伤中发挥着与IL-8不同的作用。IL-8表达与慢性丙型肝炎患者的炎症直接相关,而hIRH表达与炎症的组织病理学严重程度无关。

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