PMID- 28576828
OWN - NLM
STAT- MEDLINE
DCOM- 20170808
LR  - 20210314
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 292
IP  - 29
DP  - 2017 Jul 21
TI  - The intracellular chloride channel proteins CLIC1 and CLIC4 induce IL-1beta 
      transcription and activate the NLRP3 inflammasome.
PG  - 12077-12087
LID - S0021-9258(20)42979-5 [pii]
LID - 10.1074/jbc.M117.797126 [doi]
AB  - The NLRP3 inflammasome is a multiprotein complex that regulates the activation of 
      caspase-1 leading to the maturation of the proinflammatory cytokines IL-1beta and 
      IL-18 and promoting pyroptosis. Classically, the NLRP3 inflammasome in murine 
      macrophages is activated by the recognition of pathogen-associated molecular 
      patterns and by many structurally unrelated factors. Understanding the precise 
      mechanism of NLRP3 activation by such a wide array of stimuli remains elusive, 
      but several signaling events, including cytosolic efflux and influx of select 
      ions, have been suggested. Accordingly, several studies have indicated a role of 
      anion channels in NLRP3 inflammasome assembly, but their direct involvement has 
      not been shown. Here, we report that the chloride intracellular channel proteins 
      CLIC1 and CLIC4 participate in the regulation of the NLRP3 inflammasome. Confocal 
      microscopy and cell fractionation experiments revealed that upon LPS stimulation 
      of macrophages, CLIC1 and CLIC4 translocated into the nucleus and cellular 
      membrane. In LPS/ATP-stimulated bone marrow-derived macrophages (BMDMs), CLIC1 or 
      CLIC4 siRNA transfection impaired transcription of IL-1beta, ASC speck formation, 
      and secretion of mature IL-1beta. Collectively, our results demonstrate that CLIC1 
      and CLIC4 participate both in the priming signal for IL-1beta and in NLRP3 
      activation.
CI  - (c) 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Domingo-Fernandez, Raquel
AU  - Domingo-Fernandez R
AD  - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 
      Trinity College Dublin, Pearse Street, Dublin 2, Ireland.
FAU - Coll, Rebecca C
AU  - Coll RC
AD  - Institute for Molecular Bioscience (IMB), IMB Centre for Inflammation and Disease 
      Research, The University of Queensland, Brisbane, St Lucia, Queensland 4072, 
      Australia.
FAU - Kearney, Jay
AU  - Kearney J
AD  - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 
      Trinity College Dublin, Pearse Street, Dublin 2, Ireland.
FAU - Breit, Samuel
AU  - Breit S
AD  - St. Vincent's Centre for Applied Medical Research, St. Vincent's Hospital and 
      University of New South Wales, Sydney, New South Wales 2010, Australia.
FAU - O'Neill, Luke A J
AU  - O'Neill LAJ
AD  - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 
      Trinity College Dublin, Pearse Street, Dublin 2, Ireland. Electronic address: 
      laoneill@tcd.ie.
LA  - eng
PT  - Journal Article
DEP - 20170602
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CLIC protein, mouse)
RN  - 0 (Chloride Channels)
RN  - 0 (Clic1 protein, mouse)
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Animals
MH  - Bone Marrow Cells/cytology/drug effects/immunology/metabolism
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chloride Channels/antagonists & inhibitors/genetics/*metabolism
MH  - Inflammasomes/*drug effects/immunology/metabolism
MH  - Interleukin-1beta/*agonists/genetics/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Macrophage Activation/*drug effects
MH  - Macrophages/cytology/*drug effects/immunology/metabolism
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitochondrial Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Protein Transport/drug effects
MH  - Pyroptosis/drug effects
MH  - RAW 264.7 Cells
MH  - RNA Interference
MH  - Signal Transduction/drug effects
PMC - PMC5519359
OTO - NOTNLM
OT  - CLIC1
OT  - CLIC4
OT  - IL-1beta
OT  - NLRP3
OT  - chloride channel
OT  - inflammasome
OT  - lipopolysaccharide (LPS)
OT  - macrophage
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article
EDAT- 2017/06/04 06:00
MHDA- 2017/08/09 06:00
PMCR- 2018/07/21
CRDT- 2017/06/04 06:00
PHST- 2017/05/17 00:00 [received]
PHST- 2017/06/01 00:00 [revised]
PHST- 2017/06/04 06:00 [pubmed]
PHST- 2017/08/09 06:00 [medline]
PHST- 2017/06/04 06:00 [entrez]
PHST- 2018/07/21 00:00 [pmc-release]
AID - S0021-9258(20)42979-5 [pii]
AID - M117.797126 [pii]
AID - 10.1074/jbc.M117.797126 [doi]
PST - ppublish
SO  - J Biol Chem. 2017 Jul 21;292(29):12077-12087. doi: 10.1074/jbc.M117.797126. Epub 
      2017 Jun 2.