Τίτλος:
Neutrophil extracellular traps regulate IL-1 beta-mediated inflammation
in familial Mediterranean fever
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objective Inflammatory attacks of familial Mediterranean fever (FMF) are
characterised by circulation and influx of high number of
polymorphonuclear neutrophils (PMN) in the affected sites and profound
therapeutic effect of IL-1 beta inhibitors. We investigated the role of
neutrophil extracellular traps (NET) in the pathogenesis of FMF, and
their involvement in IL-1 beta production.
Methods Blood samples were obtained from six FMF patients during
remissions and from three patients during attacks. NET formation and NET
components were studied by fluorescence techniques, immunobloting and
MPO-DNA complex ELISA.
Results PMNs from patients released NETs decorated with IL-1 beta during
disease attacks. On the other hand, PMNs from patients during remission
were resistant to inflammatory stimuli that induce NET release in PMNs
from control subjects. Lower basal autophagy levels were identified in
PMNs during remission, while induction of autophagy facilitated NET
release, suggesting that autophagy is involved in the regulation of NET
release. During the resolution of attacks, inhibition of NET formation
by negative feedback mechanism was also observed. The anti-inflammatory
agents, colchicine and DNAse I, inhibited IL-1 beta production in PMNs
and IL-1 beta activity in NETs, respectively.
Conclusions We suggest two additive events for triggering the FMF
attack; the production of IL-1 beta by PMNs and its release through
NETs. At the same time NETs, homeostatically, downregulate further
NETosis, facilitating the resolution of attack. Compensatorly, lower
basal autophagy of PMNs may protect from crises by attenuating the
release of pro-inflammatory NETs.
Συγγραφείς:
Apostolidou, Eirini
Skendros, Panagiotis
Kambas, Konstantinos
and Mitroulis, Ioannis
Konstantinidis, Theocharis and
Chrysanthopoulou, Akrivi
Nakos, Konstantinos
Tsironidou,
Victoria
Koffa, Maria
Boumpas, Dimitrios T.
Ritis,
Konstantinos
Περιοδικό:
Annals of the Rheumatic Diseases
Εκδότης:
BMJ Publishing Group
DOI:
10.1136/annrheumdis-2014-205958
