Linked Life Data

19282652

Source:http://linkedlifedata.com/resource/pubmed/id/19282652

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-3-13
pubmed:abstractText
Innate immunity plays important roles in host defense against pathogens, but may also contribute to the development of autoimmune diseases under certain conditions. Toll-like receptors (TLRs) recognize various pathogens and induce innate immunity. We herein present a mouse model for chronic pancreatitis, which was induced by TLR3 signaling that generated the Fas/Fas ligand (FasL)-mediated cytotoxicity. An analogue of viral double-stranded RNA, polyinosinic:polycytidylic acid (poly I:C), which is recognized by TLR3, was injected into autoimmune-prone strains: MRL/Mp mice (MRL/+), MRL/Mp mice with a deficit of Fas (MRL/lpr) and MRL/Mp mice with a deficit of functional FasL (MRL/gld). The pancreatitis in MRL/+ mice was initiated by the destruction of pancreatic ductules, and its severity was significantly higher than that in MRL/lpr mice or MRL/gld mice. Using a pancreatic duct epithelial cell line MRL/S-1 newly established from the MRL/gld mouse that lacks FasL, we showed that treatment with poly I:C significantly induced the expression of Fas on the cultured cells. MRL/S-1 cells were destructed when co-cultured with splenocytes bearing intact FasL prepared from MRL/+ or MRL/lpr mice, but the magnitude of cytotoxicity was smaller with splenocytes of MRL/gld mice. Likewise, synthetic FasL protein showed cytotoxicity on MRL/S-1 cells. Furthermore, MRL/S-1 cells expressed higher levels of chemokines after the treatment with poly I:C, suggesting that the poly I:C-mediated induction of chemokines may be responsible for recruitment of lymphoid cells to the pancreatic periductular regions. These findings indicate that TLR3 signaling generates the Fas/FasL-mediated cytotoxicity, thereby leading to the development of chronic pancreatitis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1349-3329
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
217
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-84
pubmed:meshHeading
pubmed-meshheading:19282652-Animals, pubmed-meshheading:19282652-Cell Line, pubmed-meshheading:19282652-Chemokines, pubmed-meshheading:19282652-Cytotoxicity, Immunologic, pubmed-meshheading:19282652-Cytotoxicity Tests, Immunologic, pubmed-meshheading:19282652-Epithelial Cells, pubmed-meshheading:19282652-Fas Ligand Protein, pubmed-meshheading:19282652-Gene Expression Regulation, pubmed-meshheading:19282652-Immunity, Innate, pubmed-meshheading:19282652-Immunohistochemistry, pubmed-meshheading:19282652-Mice, pubmed-meshheading:19282652-Mice, Mutant Strains, pubmed-meshheading:19282652-Microarray Analysis, pubmed-meshheading:19282652-Pancreatitis, Chronic, pubmed-meshheading:19282652-Poly I-C, pubmed-meshheading:19282652-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19282652-Signal Transduction, pubmed-meshheading:19282652-Toll-Like Receptor 3
pubmed:year
2009
pubmed:articleTitle
Toll-like receptor 3 signaling induces chronic pancreatitis through the Fas/Fas ligand-mediated cytotoxicity.
pubmed:affiliation
Department of Pathogenomics, Ehime University Graduate School of Medicine, Ehime, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't