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Title of Journal: Inflamm Res

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Abbravation: Inflammation Research

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SP Birkhäuser Verlag Basel

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DOI

10.1007/s00401-005-1110-9

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1420-908X

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Calcium pyrophosphate dihydrate crystalinduced in

Authors: Tobi Higo Vince Duronio Christopher Tudan Helen M Burt John K Jackson
Publish Date: 2009/08/08
Volume: 59, Issue: 1, Pages: 71-81
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Abstract

The inflammation associated with calcium pyrophosphate dihydrate CPPD crystalinduced arthritis arises from the activation of neutrophils with crystals in the synovial joint Furthermore constitutive neutrophil apoptosis is inhibited by this interaction with CPPD so that the lifetime of the cells and the duration of the inflammatory response are extended The objective of this study was to investigate the role of bcl2 protein family members in the CPPDinduced prosurvival responseThe prosurvival proteins Mcl1 and Bclxl were both found to be strongly expressed but unaffected by CPPDinduced neutrophil activation over 3 h The expression of proapoptotic proteins Bim and Baxα was found to decrease over the time course of a 3 h incubation of neutrophils with CPPD crystals but not the bacterial chemoattractant fMLP Furthermore expression of the unphosphorylated active proapoptotic form of Bim was dominant in control cells at 05 h whereas the status of this protein switched to the phosphorylated form following cell activation by both CPPD and fMLP For CPPD but not fMLP this phosphorylation effect reversed over a 3 h incubationUpon stimulation by CPPD crystals the expression of both Bim and Baxα decreased after 3 h suggesting a reduced proapoptotic effect of these proteins so that the static expression of the prosurvival proteins Bclxl and Mcl1 might allow for a temporary shift in the balance to a prosurvival state of the cells Because a sudden but transient increase in the phosphorylated form of Bim was observed in CPPDstimulated neutrophils it is possible that this species might act as a signaling intermediate resulting in the observed downregulation of Baxα

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