Source:http://linkedlifedata.com/resource/pubmed/id/18684973
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2008-8-7
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| pubmed:abstractText |
Annexins are intracellular molecules implicated in the down-regulation of inflammation. Recently, annexin-1 has also been identified as a secreted molecule, suggesting it may have more complex effects on inflammation than previously appreciated. We studied the role of annexin-1 in mediating MMP-1 secretion from rheumatoid arthritis (RA) synovial fibroblasts (SF) stimulated with TNF-alpha. TNF-alpha induced a biphasic secretion of annexin-1 from RA SF. Early (< or = 60 min), cycloheximide-independent secretion from preformed intracellular pools was followed by late (24 h) cycloheximide-inhibitable secretion requiring new protein synthesis. Exogenous annexin-1 N-terminal peptide Ac2-26 stimulated MMP-1 secretion in a dose- (EC(50) approximately 25 microM) and time- (8-24 h) dependent manner; full-length annexin-1 had a similar effect. Down-regulation of annexin-1 using small interfering RNA resulted in decreased secretion of both annexin-1 and MMP-1, confirming that annexin-1 mediates TNF-alpha-stimulated MMP-1 secretion. Erk, Jnk, and NF-kappaB have been implicated in MMP-1 secretion. Erk, Jnk, and NF-kappaB inhibitors had no effect on annexin-1 secretion stimulated by TNF-alpha but inhibited MMP-1 secretion in response to Ac2-26, indicating that these molecules signal downstream of annexin-1. Annexin-1 stimulation of MMP-1 secretion was inhibited by both a formyl peptide receptor antagonist and pertussis toxin, suggesting that secreted annexin-1 acts via formyl peptide family receptors, most likely FPLR-1. In contrast to its commonly appreciated anti-inflammatory roles, our data indicate that annexin-1 is secreted by RA SF in response to TNF-alpha and acts in an autacoid manner to engage FPRL-1, activate Erk, Jnk, and NF-kappaB, and stimulate MMP-1 secretion.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Annexin A1,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/FPR2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Formyl Peptide,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lipoxin,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/annexin A1 peptide (2-26)
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
1550-6606
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
181
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2813-20
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:18684973-Annexin A1,
pubmed-meshheading:18684973-Arthritis, Rheumatoid,
pubmed-meshheading:18684973-Autocrine Communication,
pubmed-meshheading:18684973-Cells, Cultured,
pubmed-meshheading:18684973-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:18684973-Fibroblasts,
pubmed-meshheading:18684973-Humans,
pubmed-meshheading:18684973-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:18684973-MAP Kinase Signaling System,
pubmed-meshheading:18684973-Matrix Metalloproteinase 1,
pubmed-meshheading:18684973-NF-kappa B,
pubmed-meshheading:18684973-Peptides,
pubmed-meshheading:18684973-Receptors, Formyl Peptide,
pubmed-meshheading:18684973-Receptors, Lipoxin,
pubmed-meshheading:18684973-Synovial Membrane,
pubmed-meshheading:18684973-Tumor Necrosis Factor-alpha
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| pubmed:year |
2008
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| pubmed:articleTitle |
Annexin-1 mediates TNF-alpha-stimulated matrix metalloproteinase secretion from rheumatoid arthritis synovial fibroblasts.
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| pubmed:affiliation |
Division of Rheumatology, New York University School of Medicine/Hospital for Joint Diseases, New York, NY 10003, USA. ctagoe@montefiore.org
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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