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• W1566207114 abstract "Abstract 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-α. TNF-α induced a biphasic secretion of annexin-1 from RA SF. Early (≤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- (EC50 ≈ 25 μM) 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-α-stimulated MMP-1 secretion. Erk, Jnk, and NF-κB have been implicated in MMP-1 secretion. Erk, Jnk, and NF-κB inhibitors had no effect on annexin-1 secretion stimulated by TNF-α 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-α and acts in an autacoid manner to engage FPRL-1, activate Erk, Jnk, and NF-κB, and stimulate MMP-1 secretion." @default.
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• W1566207114 date "2008-08-15" @default.
• W1566207114 modified "2023-09-27" @default.
• W1566207114 title "Annexin-1 Mediates TNF-α-Stimulated Matrix Metalloproteinase Secretion from Rheumatoid Arthritis Synovial Fibroblasts" @default.
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• W1566207114 doi "https://doi.org/10.4049/jimmunol.181.4.2813" @default.
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