Masamune Atsushi, Kikuta Kazuhiro, Watanabe Takashi, Satoh Kennichi, Satoh Akihiko, Shimosegawa Tooru
Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
J Gastroenterol. 2008;43(5):352-62. doi: 10.1007/s00535-008-2162-0. Epub 2008 Jul 1.
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.
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.
PSCs expressed TLR2, 3, 4, and 5, as well as the associated molecules CD14 and MD2. All of the TLR ligands activated nuclear factor-kappaB, 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.
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.
Toll样受体（TLRs）是一类参与识别外来病原体相关分子模式（PAMPs）并激活固有免疫的蛋白质。本研究旨在阐明胰腺星状细胞（PSCs），即胰腺中主要的促纤维化细胞类型，是否表达TLRs并对PAMPs作出反应。
从大鼠胰腺组织中分离出PSCs，并检测TLRs的表达。用脂磷壁酸（TLR2的配体）、聚肌苷酸-聚胞苷酸（TLR3的配体）、脂多糖（TLR4的配体）或鞭毛蛋白（TLR5的配体）处理PSCs。检测TLR配体对关键细胞功能和信号通路激活的影响。还检测了PSCs进行胞吞作用和吞噬作用的能力。
PSCs表达TLR2、3、4和5，以及相关分子CD14和MD2。所有TLR配体均激活核因子-κB以及三类丝裂原活化蛋白激酶（细胞外信号调节激酶、c-Jun氨基末端激酶和p38丝裂原活化蛋白激酶）。TLR配体诱导单核细胞趋化蛋白1、细胞因子诱导的中性粒细胞趋化蛋白1（白细胞介素-8的大鼠同源物）和诱导型一氧化氮合酶的表达，但不诱导增殖或I型胶原蛋白的产生。PSCs能够进行液相和受体介导的胞吞作用，以及对大肠杆菌的吞噬作用。
PSCs表达多种TLRs并对TLR配体作出反应，导致信号通路激活和促炎反应。PSCs可通过胞吞作用和吞噬作用处理外源性抗原。PSCs可能通过识别PAMPs在胰腺的免疫功能中发挥作用。
