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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-8-7
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pubmed:abstractText |
Heat shock protein (HSP) 72 is released by cells during stress and injury. HSP-72 also stimulates the release of cytokines in macrophages by binding to Toll-like receptors (TLR) 2 and 4. Circulating levels of HSP-72 increase during hepatic ischemia-reperfusion injury. The role of extracellular HSP-72 (eHSP-72) in the injury response to ischemia-reperfusion is unknown. Therefore, the objective of the present study was to determine whether eHSP-72 has any direct effects on hepatocytes. Primary mouse hepatocytes were treated with purified human recombinant HSP-72. Conditioned media were evaluated by ELISA for the cytokines, TNF-alpha, IL-6, and macrophage inflammatory protein 2 (MIP-2). Stimulation of hepatocytes with eHSP-72 did not induce production of TNFalpha or IL-6 but resulted in dose-dependent increases in MIP-2 production. To evaluate the pathway responsible for this response, expression of TLR2 and TLR4 was confirmed on hepatocytes by immunohistochemistry. Hepatocyte production of MIP-2 was significantly decreased in hepatocytes obtained from TLR2 or TLR4 knockout mice. MIP-2 production was found to be partially dependent on NF-kappaB because inhibition of NF-kappaB with Bay 11-7085 significantly decreased eHSP-72-induced MIP-2 production. Inhibitors of p38 mitogen-activated protein kinase or c-Jun NH(2)-terminal kinase had no effect on production of MIP-2 induced by eHSP-72. The data suggest that eHSP-72 binds to TLR2 and TLR4 on hepatocytes and signals through NF-kappaB to increase MIP-2 production. The fact that eHSP-72 did not increase TNF-alpha or IL-6 production may be indicative of a highly regulated signaling pathway downstream from TLR.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-10463948,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-10742151,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-11714739,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-11717429,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-11754818,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-11836257,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-11839622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-11956372,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-11960972,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-12875976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-15191875,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-15770419,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-15857530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-16118408,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-16156712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-16200196,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-16247327,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-16343886,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-16385841,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-16387837,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-16761027,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-17027907,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-17082636,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-17185630,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-17536177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-17544402,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-17568691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-17947709,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-2250017,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-2871008,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-7525815,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-7814607,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-8413215,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-8530498,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-8637592,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-8999951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-9261113,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-9537464,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18508912-9598985
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BAY 11-7085,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Cxcl2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/HSP72 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfones,
http://linkedlifedata.com/resource/pubmed/chemical/Tlr2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tlr4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0363-6143
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
295
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C514-20
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18508912-Humans,
pubmed-meshheading:18508912-Animals,
pubmed-meshheading:18508912-Mice,
pubmed-meshheading:18508912-Liver,
pubmed-meshheading:18508912-Sulfones,
pubmed-meshheading:18508912-Mutation,
pubmed-meshheading:18508912-Peptide Fragments,
pubmed-meshheading:18508912-Nitriles,
pubmed-meshheading:18508912-Enzyme Inhibitors,
pubmed-meshheading:18508912-Hepatocytes,
pubmed-meshheading:18508912-Cells, Cultured
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