Colchicine modulates expression of pro-inflammatory genes in neutrophils from patients with familial Mediterranean fever and healthy subjects
Jazyk angličtina Země Itálie Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
23830384
PII: 6
Knihovny.cz E-zdroje
- MeSH
- dospělí MeSH
- familiární středomořská horečka farmakoterapie imunologie MeSH
- interleukin-1beta genetika MeSH
- interleukin-8 genetika MeSH
- kaspasa 1 genetika MeSH
- kolchicin farmakologie terapeutické užití MeSH
- lidé MeSH
- mladiství MeSH
- neutrofily účinky léků metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- interleukin-1beta MeSH
- interleukin-8 MeSH
- kaspasa 1 MeSH
- kolchicin MeSH
Colchicine (Col) is a microtubule depolymerizing drug, widely used for treatment of familial Mediterranean fever (FMF). Mechanisms by which Col exerts its beneficial effects are not yet completely understood, especially with respect to gene expression in polymorphonuclear neutrophils (PMNs), the main effector cells in acute inflammatory attacks of FMF. This study was, therefore, designed to elucidate possible modulatory effect of Col on expression of inflammation-related genes in circulating PMNs from 16 FMF patients in the remission period and 11 healthy subjects. In vitro effect of Col exposure (1 microg/ml) on expression of 8 selected genes was examined using quantitative real-time RT-PCR. Col up-regulated expression of IL-8 and IL-1beta genes in FMF (13-fold and 2.7-fold, p less than 0.05, respectively) and healthy (3-fold and 6.5-fold, p less than 0.05, respectively) PMNs, and down-regulated caspase-1 in FMF neutrophils (3-fold, p less than 0.05). In FMF PMNs treated with Col mRNAs of IL-8 (51-fold, p less than 0.01) and c-FOS (7-fold, p less than 0.05) transcripts were elevated compared to those from healthy subjects. By contrast, caspase-1 mRNA was decreased in FMF neutrophils compared to healthy cells (1.6-fold, p less than 0.05). Hereby, we provide evidence that, at least in vitro, Col displays pro-inflammatory potential in respect to IL-1beta and IL-8 genes. At the same time, our findings implicate suppression of caspase-1 expression by Col as a potential mechanism for its effects in FMF treatment.