Department of Immunology and Histocompatibility, Medical School, University of Thessaly, Biopolis 41110 Larissa, Greece.
Mediators Inflamm. 2011;2011:827565. doi: 10.1155/2011/827565. Epub 2011 May 25.
Patients with chronic viral hepatitis display increased expression of Foxp3 in liver, suggesting that Tregs expansion contributes to persistent infection. The purpose of this study was to elucidate whether the expression of Foxp3 relates not to the viral infection but to the resulting liver inflammation. Liver biopsies obtained from 69 individuals (26 chronic HBV hepatitis, 14 chronic HCV hepatitis, 11 nonalcoholic fatty liver disease, 8 autoimmune diseases, 2 methotrexate-related toxicity, and 8 controls) were examined, by qRT-PCR, for the mRNA expression of Foxp3, IL-10, TGF-β1, Fas, FasL, TRAIL, caspase-3, TNF-α, IFN-γ, and IL-1β. Significant increase of Foxp3 was observed in all disease groups compared to controls, which was positively correlated with the intensity of inflammation. The expression of the apoptosis mediators Fas, FasL, and TRAIL, but not of IL-10 and TGF-β1, was also significantly elevated. Our findings indicate that, independently of the initial inducer, liver inflammation is correlated with elevated expression of apoptosis mediators and is followed by local Treg accumulation. Further research towards the elucidation of the underlying casual relationships is required, in order to clarify whether our results signify the existence of a uniform Treg-mediated regulatory mechanism of apoptosis-induced inflammation.
慢性病毒性肝炎患者肝脏中 Foxp3 的表达增加，表明 Treg 的扩增有助于持续感染。本研究旨在阐明 Foxp3 的表达是否与病毒感染无关，而是与随后的肝脏炎症有关。通过 qRT-PCR 检测了 69 例个体（26 例慢性乙型肝炎、14 例慢性丙型肝炎、11 例非酒精性脂肪性肝病、8 例自身免疫性疾病、2 例甲氨蝶呤相关毒性和 8 例对照）的 Foxp3、IL-10、TGF-β1、Fas、FasL、TRAIL、caspase-3、TNF-α、IFN-γ和 IL-1β的 mRNA 表达。与对照组相比，所有疾病组的 Foxp3 表达均显著增加，且与炎症强度呈正相关。凋亡介质 Fas、FasL 和 TRAIL 的表达也显著升高，而 IL-10 和 TGF-β1 的表达则没有。我们的研究结果表明，无论初始诱导因素如何，肝脏炎症与凋亡介质的表达升高相关，随后会导致局部 Treg 积累。为了阐明我们的结果是否表明存在统一的 Treg 介导的凋亡诱导炎症的调节机制，需要进一步研究以阐明潜在的因果关系。
