| pubmed-article:19085953 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19085953 | lifeskim:mentions | umls-concept:C2340138 | lld:lifeskim |
| pubmed-article:19085953 | lifeskim:mentions | umls-concept:C1411976 | lld:lifeskim |
| pubmed-article:19085953 | lifeskim:mentions | umls-concept:C0205245 | lld:lifeskim |
| pubmed-article:19085953 | lifeskim:mentions | umls-concept:C0023745 | lld:lifeskim |
| pubmed-article:19085953 | lifeskim:mentions | umls-concept:C1704632 | lld:lifeskim |
| pubmed-article:19085953 | lifeskim:mentions | umls-concept:C0871261 | lld:lifeskim |
| pubmed-article:19085953 | lifeskim:mentions | umls-concept:C0752046 | lld:lifeskim |
| pubmed-article:19085953 | lifeskim:mentions | umls-concept:C2911692 | lld:lifeskim |
| pubmed-article:19085953 | lifeskim:mentions | umls-concept:C1706817 | lld:lifeskim |
| pubmed-article:19085953 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:19085953 | pubmed:dateCreated | 2009-3-3 | lld:pubmed |
| pubmed-article:19085953 | pubmed:abstractText | In a recent study, a single nucleotide polymorphism (SNP) of the Toll-like receptor 4 (TLR4) gene (c.1196C>T [rs4986791, p.T399I]) emerged as conferring protection from fibrosis progression compared to a major, wild-type (WT) CC allele (p.T399). The present study examined the functional linkage of this SNP, along with another common, highly cosegregated TLR4 SNP (c.896A>G [rs4986790, p.D299G]), to hepatic stellate cell (HSC) responses. Both HSCs from TLR4(-/-) mice and a human HSC line (LX-2) reconstituted with either TLR4 D299G and/or T399I complementary DNAs were hyporesponsive to lipopolysaccharide (LPS) stimulation compared to those expressing WT TLR4, as assessed by the expression and secretion of LPS-induced inflammatory and chemotactic cytokines (i.e., monocyte chemoattractant protein-1, interleukin-6), down-regulation of bone morphogenic protein and the activin membrane-bound inhibitor expression (an inhibitory transforming growth factor beta pseudoreceptor), and activation of a nuclear factor kappaB (NF-kappaB)-responsive luciferase reporter. In addition, spontaneous apoptosis, as well as apoptosis induced by pathway inhibitors of NF-kappaB, extracellular signal-regulated kinase (ERK), and phosphatidylinositol 3-kinase were greatly increased in HSCs from either TLR4(-/-) or myeloid differentiation factor 88(-/-) (a TLR adaptor protein) mice, as well as in murine HSCs expressing D299G and/or T399I SNPs; increased apoptosis in these lines was accompanied by decreased phospho-ERK and Bcl-2. CONCLUSION: TLR4 D299G and T399I SNPs that are associated with protection from hepatic fibrosis reduce TLR4-mediated inflammatory and fibrogenic signaling and lower the apoptotic threshold of activated HSCs. These findings provide a mechanistic link that explains how specific TLR4 SNPs may regulate the risk of fibrosis progression. | lld:pubmed |
| pubmed-article:19085953 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19085953 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19085953 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19085953 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:19085953 | pubmed:issn | 1527-3350 | lld:pubmed |
| pubmed-article:19085953 | pubmed:author | pubmed-author:FriedmanScott... | lld:pubmed |
| pubmed-article:19085953 | pubmed:author | pubmed-author:HongFengF | lld:pubmed |
| pubmed-article:19085953 | pubmed:author | pubmed-author:ZhengFengF | lld:pubmed |
| pubmed-article:19085953 | pubmed:author | pubmed-author:SninskyJohn... | lld:pubmed |
| pubmed-article:19085953 | pubmed:author | pubmed-author:FukataMasayuk... | lld:pubmed |
| pubmed-article:19085953 | pubmed:author | pubmed-author:TarocchiMirko... | lld:pubmed |
| pubmed-article:19085953 | pubmed:author | pubmed-author:YeaStevenS | lld:pubmed |
| pubmed-article:19085953 | pubmed:author | pubmed-author:HuangHongjinH | lld:pubmed |
| pubmed-article:19085953 | pubmed:author | pubmed-author:AbarOlivia... | lld:pubmed |
| pubmed-article:19085953 | pubmed:author | pubmed-author:GuoJinshengJ | lld:pubmed |
| pubmed-article:19085953 | pubmed:author | pubmed-author:LokeJohnnyJ | lld:pubmed |
| pubmed-article:19085953 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19085953 | pubmed:volume | 49 | lld:pubmed |
| pubmed-article:19085953 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19085953 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19085953 | pubmed:pagination | 960-8 | lld:pubmed |
| pubmed-article:19085953 | pubmed:dateRevised | 2010-9-23 | lld:pubmed |
| pubmed-article:19085953 | pubmed:meshHeading | pubmed-meshheading:19085953... | lld:pubmed |
| pubmed-article:19085953 | pubmed:meshHeading | pubmed-meshheading:19085953... | lld:pubmed |
| pubmed-article:19085953 | pubmed:meshHeading | pubmed-meshheading:19085953... | lld:pubmed |
| pubmed-article:19085953 | pubmed:meshHeading | pubmed-meshheading:19085953... | lld:pubmed |
| pubmed-article:19085953 | pubmed:meshHeading | pubmed-meshheading:19085953... | lld:pubmed |
| pubmed-article:19085953 | pubmed:meshHeading | pubmed-meshheading:19085953... | lld:pubmed |
| pubmed-article:19085953 | pubmed:meshHeading | pubmed-meshheading:19085953... | lld:pubmed |
| pubmed-article:19085953 | pubmed:meshHeading | pubmed-meshheading:19085953... | lld:pubmed |
