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Published on: March 3, 2015
The effect of colchicine on pyrin and pyrin interacting proteins
Ekim Z Taskiran1, Arda Cetinkaya, Banu Balci-Peynircioglu
1Department of Medical Biology, Hacettepe University, Ankara, Turkey.
Abstract:
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.
Insights
Colchicine, a treatment for familial Mediterranean fever (FMF), impacts pyrin and its related proteins. This study reveals colchicine affects actin cytoskeleton organization and MEFV gene expression, potentially explaining its efficacy in FMF.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- Familial Mediterranean fever (FMF) is the most common autoinflammatory disease, caused by mutations in the MEFV gene encoding pyrin.
- Pyrin's role in inflammation regulation is not fully understood, and the precise mechanism of colchicine's efficacy in FMF is unclear.
- Colchicine, a microtubule inhibitor, is a highly effective prophylactic treatment for FMF.
Purpose of the Study:
- To investigate the specific cellular mechanisms underlying colchicine's efficacy in FMF.
- To explore the potential direct effects of colchicine on pyrin and its interacting proteins.
- To elucidate the connection between colchicine, pyrin, and the MEFV gene.
Main Methods:
- Investigated the effect of colchicine on PSTPIP1 filaments and ASC speck formation in transfected cells.
- Analyzed MEFV gene expression in THP-1 cells treated with colchicine.
- Examined the impact of colchicine on the actin cytoskeleton organization in THP-1 cells.
Main Results:
- Colchicine treatment inhibited the formation of reticulated fibrils by PSTPIP1 filaments and reduced ASC speck rates.
- Colchicine was found to down-regulate MEFV gene expression in THP-1 cells.
- Colchicine induced significant re-organization of the actin cytoskeleton in THP-1 cells, where pyrin is an actin-binding protein.
Conclusions:
- Colchicine's efficacy in FMF may be linked to its effects on pyrin-interacting proteins and the actin cytoskeleton.
- Down-regulation of MEFV expression by colchicine, potentially mediated by actin cytoskeleton changes, could explain its therapeutic benefit.
- This study highlights a novel connection between colchicine and pyrin, offering insights into FMF pathogenesis and treatment.
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