Pancreatic stellate cells express Toll-like receptors
Pancreatic stellate cells express Toll-like receptors
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DOI：
10.1007/s00535-008-2162-0
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发表时间：
2008-01-01
影响因子：
6.3
通讯作者：
Shimosegawa, Tooru
中科院分区：
文献类型：
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作者：
Masamune, Atsushi;Kikuta, Kazuhiro;Shimosegawa, Tooru
研究背景Toll样受体（Toll like receptor，TLR）是一类参与识别外源病原体相关分子模式（PAMPs）和激活先天免疫的蛋白质。本研究旨在阐明胰腺星状细胞（PSC），胰腺中主要的促纤维化细胞类型，是否表达TLR并对PAMP产生应答。方法.从大鼠胰腺组织中分离PSC，并检测TLR的表达。用脂磷壁酸（TLR 2的配体）、聚肌苷酸-聚胞苷酸（TLR 3的配体）、脂多糖（TLR 4的配体）或鞭毛蛋白（TLR 5的配体）处理PSC。检查TLR配体对关键细胞功能和信号传导途径活化的影响。还检查了PSC进行内吞作用和吞噬作用的能力。结果PSC表达TLR 2、3、4和5，以及相关分子CD 14和MD 2。所有TLR配体激活核因子-κ B和三类促分裂原活化蛋白激酶（细胞外信号调节激酶、c-Jun N-末端激酶和p38促分裂原活化蛋白激酶）。TLR配体诱导表达单核细胞趋化蛋白1，白细胞介素诱导的中性粒细胞趋化因子1（大鼠白细胞介素-8同源物），诱导型一氧化氮合酶，但不增殖或I型胶原蛋白的生产。PSC可以进行液相和受体介导的内吞，以及大肠杆菌的吞噬。结论. PSC表达多种TLR并对TLR配体产生应答，导致信号通路的激活和促炎反应。PSCs可通过内吞和吞噬作用加工外源性抗原。PSCs可能通过识别PAMPs参与胰腺的免疫功能。
Background Toll-like receptors (TLRs) are proteins involved in recognition of foreign pathogen-associated molecular patterns (PAMPs) and activation of innate immunity. This study aimed to clarify whether pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, expressed TLRs and responded to PAMPs. Methods. PSCs were isolated from rat pancreas tissue, and expression of TLRs was examined. PSCs were treated with lipoteichoic acid (a ligand for TLR2), polyinosinic-polycytidylic acid (a ligand for TLR3), lipopolysaccharide (a ligand for TLR4), or flagellin (a ligand for TLR5). The effects of the TLR ligands on key cell functions and activation of signaling pathways were examined. The ability of PSCs to perform endocytosis and phagocytosis was also examined. Results. PSCs expressed TLR2, 3, 4, and 5, as well as the associated molecules CD14 and MD2. All of the TLR ligands activated nuclear factor-kappa B, and three classes of mitogen-activated protein kinases (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase). TLR ligands induced expression of monocyte chemoattractant protein 1, cytokine-induced neutrophil chemoattractant 1 (a rat homolog of interleukin-8), and inducible nitric oxide synthase, but not proliferation or type I collagen production. PSCs could perform fluid-phase and receptor-mediated endocytosis, as well as phagocytosis of Escherichia coli. Conclusions. PSCs expressed a variety of TLRs and responded to TLR ligands, leading to the activation of signaling pathways and proinflammatory responses. PSCs could process exogenous antigens by endocytosis and phagocytosis. PSCs might play a role in the immune functions of the pancreas through the recognition of PAMPs.