当前位置： SCI文献检索 > BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS期刊下所有文献 > The nuclear receptor and clock gene REV-ERBα regulates cigarette smoke-induced lung inflammation.

The nuclear receptor and clock gene REV-ERBα regulates cigarette smoke-induced lung inflammation.

Abstract：

:REV-ERBα is a nuclear heme receptor, transcriptional repressor and critical component of the molecular clock that drives daily rhythms of metabolism. Evidence reveals that REV-ERBα also plays an important regulatory role in clock-dependent lung physiology and inflammatory responses. We hypothesize that cigarette smoke (CS) exposure influences REV-ERBα abundance in the lungs, facilitating a pro-inflammatory phenotype. To determine the impact of REV-ERBα 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-ERBα agonist GSK 4112. We also exposed adult C57BL/6J (WT) and Rev-erbα 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-ERBα 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-ERBα is a critical regulator of CS-induced lung inflammatory responses.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Sundar IK,Rashid K,Sellix MT,Rahman I

doi

10.1016/j.bbrc.2017.09.157

subject

Has Abstract

pub_date

2017-12-02 00:00:00

pages

1390-1395

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(17)31945-9

journal_volume

493

pub_type

杂志文章

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