The effect of colchicine on pyrin and pyrin interacting proteins.
J Cell Biochem
; 113(11): 3536-46, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-22730186
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citoesqueleto de Actina
/
Colchicina
/
Proteínas do Citoesqueleto
/
Proteínas Adaptadoras de Transdução de Sinal
/
Moduladores de Tubulina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Biochem
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Turquia