| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
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. PSC 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 were examined on the activation of nuclear factor-κB and mitogen-activated protein kinases, chemokine production, and expression of inducible nitric oxide synthase. The ability to perform endocytosis and phagocytosis was also examined. PSCs expressed TLR2, 3, 4, and 5, as well as associated molecules CD14 and MD2. All of the TLR ligands activated nuclear factor-κB 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 the expression of monocyte chemoattractant protein-1, cytokine-induced neutrophil chemoattractant-1, and inducible nitric oxide synthase. PSCs could perform fluid-phase and receptor-mediated endocytosis, as well as phagocytosis of E. coli. In conclusion, 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.
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