PMID- 28974420
OWN - NLM
STAT- MEDLINE
DCOM- 20171030
LR  - 20181202
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 493
IP  - 4
DP  - 2017 Dec 2
TI  - The nuclear receptor and clock gene REV-ERBalpha regulates cigarette smoke-induced 
      lung inflammation.
PG  - 1390-1395
LID - S0006-291X(17)31945-9 [pii]
LID - 10.1016/j.bbrc.2017.09.157 [doi]
AB  - REV-ERBalpha is a nuclear heme receptor, transcriptional repressor and critical 
      component of the molecular clock that drives daily rhythms of metabolism. 
      Evidence reveals that REV-ERBalpha also plays an important regulatory role in 
      clock-dependent lung physiology and inflammatory responses. We hypothesize that 
      cigarette smoke (CS) exposure influences REV-ERBalpha abundance in the lungs, 
      facilitating a pro-inflammatory phenotype. To determine the impact of REV-ERBalpha 
      activation in the CS-induced inflammatory response we treated primary human small 
      airway epithelial cells (SAECs) with CS extract (CSE) or lipopolysaccharide (LPS) 
      in the absence or presence of pre-treatment with the REV-ERBalpha agonist GSK 4112. 
      We also exposed adult C57BL/6J (WT) and Rev-erbalpha global KO mice to CS (10 and 30 
      days) and measured pro-inflammatory cytokine release. Our data reveal that 
      pre-treatment with GSK 4112 reduced CSE/LPS induced pro-inflammatory cytokines 
      release from both SAECs and mouse lung fibroblasts (MLFs). Furthermore, REV-ERBalpha 
      KO mice show a greater inflammatory response to 10 and 30 days of CS, including 
      increased neutrophil lung influx, pro-inflammatory cytokine (IL-6, MCP-1 and KC) 
      release, and pro-senescence marker (p16) when compared to WT mice. These data 
      demonstrate that REV-ERBalpha is a critical regulator of CS-induced lung inflammatory 
      responses.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Sundar, Isaac K
AU  - Sundar IK
AD  - Department of Environmental Medicine, University of Rochester Medical Center, 
      Rochester, NY, USA.
FAU - Rashid, Kahkashan
AU  - Rashid K
AD  - Department of Environmental Medicine, University of Rochester Medical Center, 
      Rochester, NY, USA.
FAU - Sellix, Michael T
AU  - Sellix MT
AD  - Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, 
      University of Rochester Medical Center, Rochester, NY, USA.
FAU - Rahman, Irfan
AU  - Rahman I
AD  - Department of Environmental Medicine, University of Rochester Medical Center, 
      Rochester, NY, USA. Electronic address: irfan_rahman@urmc.rochester.edu.
LA  - eng
GR  - R01 HL135613/HL/NHLBI NIH HHS/United States
GR  - R01 HL085613/HL/NHLBI NIH HHS/United States
GR  - R01 HL133404/HL/NHLBI NIH HHS/United States
GR  - R56 ES027012/ES/NIEHS NIH HHS/United States
GR  - R01 HL137738/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20170930
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cytokines)
RN  - 0 (GSK4112)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NR1D1 protein, human)
RN  - 0 (Nr1d1 protein, mouse)
RN  - 0 (Nuclear Receptor Subfamily 1, Group D, Member 1)
RN  - 0 (Smoke)
RN  - 0 (Thiophenes)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Epithelial Cells/drug effects/metabolism/pathology
MH  - Female
MH  - Glycine/analogs & derivatives/pharmacology
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Lung/drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neutrophil Infiltration
MH  - Nuclear Receptor Subfamily 1, Group D, Member 
      1/agonists/deficiency/*genetics/metabolism
MH  - Pneumonia/*etiology/*genetics/metabolism
MH  - Smoke/adverse effects
MH  - Smoking/*adverse effects/genetics/metabolism
MH  - Thiophenes/pharmacology
PMC - PMC5756581
MID - NIHMS928830
OTO - NOTNLM
OT  - COPD
OT  - Cellular senescence
OT  - Cytokines
OT  - Molecular clock
OT  - Oxidants
OT  - REV-ERBalpha
COIS- Conflicts of interest No conflicts of interest, financial or otherwise, are 
      declared by the author(s).
EDAT- 2017/10/05 06:00
MHDA- 2017/10/31 06:00
PMCR- 2018/12/02
CRDT- 2017/10/05 06:00
PHST- 2017/09/25 00:00 [received]
PHST- 2017/09/28 00:00 [accepted]
PHST- 2017/10/05 06:00 [pubmed]
PHST- 2017/10/31 06:00 [medline]
PHST- 2017/10/05 06:00 [entrez]
PHST- 2018/12/02 00:00 [pmc-release]
AID - S0006-291X(17)31945-9 [pii]
AID - 10.1016/j.bbrc.2017.09.157 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2017 Dec 2;493(4):1390-1395. doi: 
      10.1016/j.bbrc.2017.09.157. Epub 2017 Sep 30.