Pancreatic stellate cells express Toll-like receptors.
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-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.


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.
Masamune
Atsushi
A
Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Kikuta
Kazuhiro
K
Watanabe
Takashi
T
Satoh
Kennichi
K
Satoh
Akihiko
A
Shimosegawa
Tooru
T
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D007113:Immunity, Innate / Q000235:genetics; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D051218:Lymphocyte Antigen 96 / Q000276:immunology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D010179:Pancreas / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000235:genetics; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics; D051198:Toll-Like Receptor 5 / Q000096:biosynthesis / Q000235:genetics; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics*
D018932:Chemokine CCL2; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D012313:RNA; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases