Mozer-Lisewska I, Sluzewski W, Kaczmarek M, Jenek R, Szczepanski M, Figlerowicz M, Kowala-Piaskowska A, Zeromski J
Department of Infectious Diseases and Child Neurology, University of Medical Sciences, Poznan, Poland.
Scand J Immunol. 2005 Oct;62(4):407-12. doi: 10.1111/j.1365-3083.2005.01670.x.
Toll-like receptors (TLR) are important tools of innate immunity, localized mainly on cells of the immune system, but also have been shown on cells of other origin. In the current study, they have been searched in biopsy specimens of liver from children bearing chronic viral hepatitis of C type (HCV). TLR2, TLR3 and TLR4 were traced by means of polyclonal antibodies and avidin-biotin complex (ABC) immunohistochemistry. Besides, mRNA for TLR was looked for using specific primers and polymerase chain reaction. Several controls, including neutralization of primary antibody with respective blocking peptide, confirmed the specificity of the immunohistochemical reaction. All TLR tested could be visualized in a focal distribution in single hepatocytes and some cells of inflammatory infiltrates. There was no reaction whatsoever in liver samples not infected with hepatotropic virus. In molecular studies, mRNA for TLR2 and TLR4 was detected in both noninfected and hepatitis B virus-infected established cell lines of human hepatoma as well as in HCV(+) biopsy samples. These data indicate that TLR can be traced in liver cells, both at the protein and at the mRNA level. Their irregular and focal distribution in HCV(+), but not in HCV(-), liver suggests some role of TLR in the pathogenesis of chronic viral hepatitis, at least in children.
Toll样受体（TLR）是天然免疫的重要工具，主要定位于免疫系统细胞，但也已在其他来源的细胞中发现。在本研究中，对患有慢性丙型病毒性肝炎（HCV）儿童的肝脏活检标本进行了检测。采用多克隆抗体和抗生物素蛋白-生物素复合物（ABC）免疫组织化学法追踪TLR2、TLR3和TLR4。此外，使用特异性引物和聚合酶链反应寻找TLR的mRNA。包括用相应封闭肽中和一抗在内的多个对照证实了免疫组织化学反应的特异性。所有检测的TLR均可在单个肝细胞和一些炎性浸润细胞中呈局灶性分布显现出来。在未感染嗜肝病毒的肝脏样本中未出现任何反应。在分子研究中，在人肝癌的未感染及乙型肝炎病毒感染的既定细胞系以及HCV（+）活检样本中均检测到了TLR2和TLR4的mRNA。这些数据表明，在肝细胞中，无论是在蛋白质水平还是mRNA水平，均可追踪到TLR。它们在HCV（+）而非HCV（-）肝脏中的不规则局灶性分布提示，至少在儿童中，TLR在慢性病毒性肝炎的发病机制中发挥了一定作用。
