Effect of colchicine on expression of inflammation-related genes in neutrophils from healthy subjects and patients with familial Mediterranean feve
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1
Palacky University, Laboratory of Immunogenomics and Immunoproteomics, Faculty of Medicine and Dentistry, Czechia
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2
Institute of Molecular Biology, National Academy of Sciences, Group of Molecular and Cellular Immunology, Armenia
Despite the long-standing use of antimitotic drug colchicine in the treatment of familial Mediterranean fever (FMF) the precise mechanisms of its action in polymorphonuclear neutrophils (PMNs) remain largely unknown. Colchicine is a microtubule depolymerizing agent which arrests microtubule assembly and inhibits many cellular functions. FMF is a hereditary autoinflammatory disorder characterized by abnormal activation of PMNs and their unprovoked influx into the affected sites. This study aimed to analyze transcriptional events elicited by colchicine in PMNs isolated from the peripheral blood of 16 FMF patients in the remission period and 11 healthy control subjects by determining mRNAs expression of 8 selected genes using quantitative real-time RT-PCR. Colchicine exposure (1µg/ml) elicited up-regulated expression of IL-8 and IL-1β genes in FMF (13-fold and 2.7-fold, p<0.05, respectively) and healthy (3-fold and 6.5-fold, p<0.05, respectively) PMNs, and at the same time in down-regulated caspase-1 in FMF PMNs (3-fold, p<0.05). In FMF PMNs treated with colchicines, mRNAs of IL-8 (51-fold, p<0.01) and c-FOS (7-fold, p<0.05) were elevated compared to cells from control subjects. By contrast, caspase-1 mRNA was decreased in FMF PMNs compared control cells (1.6-fold, p<0.05). Thus, we provide in vitro evidence of colchicine modulatory role on expression of inflammation-related genes at the transcriptional level. The up-regulation of IL-1β and IL-8 suggests that colchicine can, besides its well-known anti-inflammatory properties, exhibit pro-inflammatory features. Finally, suppressed caspase-1 expression by colchicine could represent a therapeutic target and may be implicated in effective therapy of FMF.
Acknowledgements
Acknowledgment: IGA PU LF 2012_007, 2013_0
Keywords:
Colchicine,
Familial Mediterranean Fever,
Neutrophils,
caspase-1,
IL-1β
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Manukyan
G,
Petrek
M,
Martirosyan
A,
Navratilova
Z and
Kriegova
E
(2013). Effect of colchicine on expression of inflammation-related genes in neutrophils from healthy subjects and patients with familial Mediterranean feve.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00616
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Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Gayane Manukyan, Palacky University, Laboratory of Immunogenomics and Immunoproteomics, Faculty of Medicine and Dentistry, Olomouc, Czechia, gaya.manukyan@gmail.com