Interferon gamma accelerates NF-kappaB activation of biliary epithelial cells induced by Toll-like receptor and ligand interaction.
Interferon gamma accelerates NF-kappaB activation of biliary epithelial cells induced by Toll-like receptor and ligand interaction.
复制标题
DOI：
--
复制
发表时间：
2006
影响因子：
3.4
通讯作者：
K. Harada;K. Isse;Y. Nakanuma
中科院分区：
文献类型：
--
作者：
K. Harada;K. Isse;Y. Nakanuma
Toll样受体（TLR）家族识别病原体相关分子模式（PAMP），并在先天免疫应答中起关键作用。肝内胆管内衬的胆管上皮细胞（BEC）可能暴露于胆汁中的细菌成分，并且小鼠BEC具有识别PAMP的TLR，导致核因子κ B（NF-κ B）活化。目的检测人BEC中TLR的存在以及细胞因子和PAMP对TLR表达和NF-κ B活化的影响。方法采用免疫组化和逆转录聚合酶链反应（RT-PCR）方法检测TLR 2 -5、MD-2、MyD 88和IRAK 1在人肝组织和培养的BECs中的表达。通过NF-κ B活化评估PAMP（肽聚糖和脂多糖）在用干扰素γ（IFN γ）预孵育的培养细胞中的影响。结果TLR 2 -5、MyD 88和IRAK-1蛋白在人肝内胆管树BEC中均有表达。TLR 2 -5、MD-2、MyD 88和IRAK-1 mRNA在人培养的BEC中被证实。这些TLR的表达被IFN γ上调，并且TLR 2被肿瘤坏死因子α上调。白细胞介素4和6未能诱导TLR上调。有趣的是，在培养的BEC中，与IFN γ预孵育协同增加PAMP诱导的NF-κ B的上调。结论TLR家族存在于人胆管细胞中，并参与肝内胆管系统的天然免疫。细胞因子和PAMP的细胞内信号传导后TLR的失调可能参与免疫介导的胆道疾病。
BACKGROUND The Toll-like receptor (TLR) family recognises pathogen associated molecular patterns (PAMPs) and plays a pivotal role in the innate immune response. Biliary epithelial cells (BECs) lining the intrahepatic bile ducts are potentially exposed to bacterial components in bile, and murine BECs possess TLRs that recognise PAMPs, resulting in nuclear factor kappaB (NF-kappaB) activation. AIMS To examine the presence of TLRs in human BECs and the influence of cytokines and PAMPs on TLR expression and NF-kappaB activation. METHODS The expression of TLR2-5, MD-2, MyD88, and IRAK1 was examined in human liver tissue and cultured BECs by immunohistochemistry or reverse transcription polymerase chain reaction. The influence of PAMPs (peptidoglycan and lipopolysaccharide) in cultured cells preincubated with interferon gamma (IFNgamma) was evaluated by NF-kappaB activation. RESULTS TLR2-5, MyD88, and IRAK-1 proteins were detectable in BECs of the intrahepatic biliary tree in human liver tissue. TLR2-5, MD-2, MyD88, and IRAK-1 mRNA was demonstrated in human cultured BECs. The expression of these TLRs was upregulated by IFNgamma, and TLR2 was upregulated by tumour necrosis factor alpha. Interleukins 4 and 6 failed to induce TLR upregulation. Interestingly, preincubation with IFNgamma synergistically increased the upregulation of NF-kappaB induced by PAMPs in cultured BECs. CONCLUSION These results suggest that the TLR family is present in human biliary cells and participates in the innate immunity of the intrahepatic biliary tree. Disordered regulation of TLRs after intracellular signalling by cytokines and PAMPs may be involved in immune mediated biliary diseases.