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  • Familial Mediterranean fever (FMF) is autoinflammatory disorder, characterized by MEFV gene mutations and recurrent episodes of fever and serosal or synovial inflammation. Neutrophils are the predominant effector cells of acute inflammatory attacks in FMF; however pathogenic role and molecular phenotype of these cells remain largely unknown. To gain insight into the processes that contribute to the self-directed autoinflammation we characterized expression of a spectrum of genes involved in regulation of inflammation in unstimulated and LPS-activated neutrophils from FMF patients. Expression of 12 candidate immune genes encoding for inflammation-related molecules was assessed by quantitative RT-PCR in freshly isolated and LPS-stimulated peripheral polymorphonuclear neutrophils from fifteen FMF patients in attack-free period and ten healthy volunteers as controls. The relative expression was calculated using the second derivative method; the target gene expression was normalized to the expression of RPL32 gene. FMF neutrophils were characterized by up-regulated baseline gene expression of c-FOS (9.5-fold, p { 0.05), IL-8 (12-fold, p { 0.05), MMP9 (8-fold, p { 0.01), TLR2 (7-fold, p { 0.05) compared to the neutrophils from control subjects, a trend was also evident towards increased caspase-1 expression (3-fold, p = 0.09). Discriminant analysis clustered the patient and control subjects into two distinct groups (Wilks's lambda = 0.165, p = 0.042). Further, LPS-induced alterations of expression profiles were shared between FMF and healthy neutrophils, the profile consisting namely of up-regulated IL-1 beta, TLR4, IL-8, and TNFAIP6 transcripts. Present study demonstrates distinct expression patterns of pre-activated neutrophils during attack-free period of FMF when compared to neutrophils from healthy controls. Furthermore, our data emphasize the importance of host-derived ligands in activation of FMF neutrophils. (C) 2012 Elsevier GmbH. All rights reserved.
  • Familial Mediterranean fever (FMF) is autoinflammatory disorder, characterized by MEFV gene mutations and recurrent episodes of fever and serosal or synovial inflammation. Neutrophils are the predominant effector cells of acute inflammatory attacks in FMF; however pathogenic role and molecular phenotype of these cells remain largely unknown. To gain insight into the processes that contribute to the self-directed autoinflammation we characterized expression of a spectrum of genes involved in regulation of inflammation in unstimulated and LPS-activated neutrophils from FMF patients. Expression of 12 candidate immune genes encoding for inflammation-related molecules was assessed by quantitative RT-PCR in freshly isolated and LPS-stimulated peripheral polymorphonuclear neutrophils from fifteen FMF patients in attack-free period and ten healthy volunteers as controls. The relative expression was calculated using the second derivative method; the target gene expression was normalized to the expression of RPL32 gene. FMF neutrophils were characterized by up-regulated baseline gene expression of c-FOS (9.5-fold, p { 0.05), IL-8 (12-fold, p { 0.05), MMP9 (8-fold, p { 0.01), TLR2 (7-fold, p { 0.05) compared to the neutrophils from control subjects, a trend was also evident towards increased caspase-1 expression (3-fold, p = 0.09). Discriminant analysis clustered the patient and control subjects into two distinct groups (Wilks's lambda = 0.165, p = 0.042). Further, LPS-induced alterations of expression profiles were shared between FMF and healthy neutrophils, the profile consisting namely of up-regulated IL-1 beta, TLR4, IL-8, and TNFAIP6 transcripts. Present study demonstrates distinct expression patterns of pre-activated neutrophils during attack-free period of FMF when compared to neutrophils from healthy controls. Furthermore, our data emphasize the importance of host-derived ligands in activation of FMF neutrophils. (C) 2012 Elsevier GmbH. All rights reserved. (en)
Title
  • Activated phenotype of circulating neutrophils in familial Mediterranean fever
  • Activated phenotype of circulating neutrophils in familial Mediterranean fever (en)
skos:prefLabel
  • Activated phenotype of circulating neutrophils in familial Mediterranean fever
  • Activated phenotype of circulating neutrophils in familial Mediterranean fever (en)
skos:notation
  • RIV/61989592:15110/13:33143924!RIV14-MSM-15110___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • S
http://linked.open...iv/cisloPeriodika
  • 6
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 59382
http://linked.open...ai/riv/idVysledku
  • RIV/61989592:15110/13:33143924
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • TLR2.; RT-PCR; Polymorphonuclear neutrophils; LPS; Familial Mediterranean fever; c-FOS; Caspase-1 (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • DE - Spolková republika Německo
http://linked.open...ontrolniKodProRIV
  • [4C7EBE9FCBC2]
http://linked.open...i/riv/nazevZdroje
  • Immunobiology
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 218
http://linked.open...iv/tvurceVysledku
  • Boyajyan, Anna
  • Kriegová, Eva
  • Petřek, Martin
  • Fillerová, Regina
  • Ghazaryan, Karine
  • Manukyan, Gayane
http://linked.open...ain/vavai/riv/wos
  • 000319486200008
issn
  • 0171-2985
number of pages
http://bibframe.org/vocab/doi
  • 10.1016/j.imbio.2012.10.007
http://localhost/t...ganizacniJednotka
  • 15110
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