The effect of colchicine on pyrin and pyrin interacting proteins.
MEFV which encodes pyrin, cause familial Mediterranean fever (FMF), the most common auto-inflammatory disease. Pyrin is believed to be a regulator of inflammation, though the nature of this regulatory activity remains to be identified. Prophylactic treatment with colchicine, a microtubule toxin, has had a remarkable effect on disease progression and outcome. It has been thought that, inhibition of microtubule polymerization is the main mechanism of action of colchicine. But, the exact cellular mechanism explaining the efficacy of colchicine in suppressing FMF attacks is still unclear. Given the ability of colchicine treatment to be considered as a differential diagnosis criteria of FMF, we hypothesized that colchicine may have a specific effect on pyrin and pyrin interacting proteins. This study showed that colchicine prevents reticulated fibrils formed by PSTPIP1 filaments and reduces ASC speck rates in transfected cells. We further noted that, colchicine down-regulates MEFV expression in THP-1 cells. We also observed that colchicine causes re-organization of actin cytoskeleton in THP-1 cells. Pyrin is an actin-binding protein that specifically localizes with polymerizing actin filaments. Thus, MEFV expression might be affected by re-organization of actin cytoskeleton. The data presented here reveal an important connection between colchicine and pyrin which might explain the remarkable efficacy of colchicine in preventing FMF attacks.
Department of Medical Biology, Hacettepe University, Ankara, Turkey.
Ekim Z
EZ
Taskiran
Arda
A
Cetinkaya
Banu
B
Balci-Peynircioglu
Yeliz Z
YZ
Akkaya
Engin
E
Yilmaz
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003078:Colchicine / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D000071198:Pyrin; D014162:Transfection; D050257:Tubulin Modulators / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; C486382:PSTPIP1 protein, human; D000071198:Pyrin; D050257:Tubulin Modulators; D049452:Green Fluorescent Proteins; D003078:Colchicine