title: Transcriptional activity of neutrophils exposed to high doses of colchicine: short communication.
abstract: Colchicine is an antimitotic drug which binds to tubulin and at high doses results in cytoskeleton disruption. Colchicine is believed to be an anti-inflammatory agent, though its modulatory effects on the level and transcriptional activity of genes is still a matter of debate. There is growing evidence that alterations in the cytoskeleton exert specific effects on the expression of various genes. This study was undertaken to analyze whether disrupting the microtubule cytoskeleton by colchicine modulates transcriptional levels of MEFV, NF-κB p65, NLRP3, HMGB1, and caspase-3 in neutrophils from patients with familial Mediterranean fever (FMF) and healthy subjects. In the present study, colchicine caused increased expression of NLRP3 (p=0.007) and MEFV (p=0.03), but had no effect on caspase-3, NF-κB p65 and HMGB1 genes in healthy neutrophils. FMF neutrophils were less responsive to the drug treatment. This study supports the hypothesis that, being an anti-inflammatory agent, colchicine at relatively high concentrations might lead to the activation of pro-inflammatory signalling pathways in neutrophils.
authors: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors: G
authors: G
authors: Manukyan
authors: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors: M
authors: M
authors: Petrek
authors: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors: Z
authors: Z
authors: Navratilova
authors: Group of Molecular and Cellular Immunology, Institute of Molecular Biology, National Academy of Sciences, Yerevan, Armenia.
authors: S
authors: S
authors: Margaryan
authors: Laboratory of Macromolecular Complexes, Institute of Molecular Biology, National Academy of Sciences, Yerevan, Armenia.
authors: A
authors: A
authors: Boyajyan
mesh_terms: D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D010505:Familial Mediterranean Fever / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D024243:HMGB1 Protein / Q000235:genetics; D006801:Humans; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D000071198:Pyrin; D051996:Transcription Factor RelA / Q000235:genetics; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C000604192:MEFV protein, human; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D000071198:Pyrin; C498143:RELA protein, human; D051996:Transcription Factor RelA; C505407:CASP3 protein, human; D053148:Caspase 3; D003078:Colchicine