Format

Send to

Choose Destination
Toxicol Lett. 2014 Apr 21;226(2):107-16. doi: 10.1016/j.toxlet.2014.01.020. Epub 2014 Jan 25.

The NF-κB family member RelB regulates microRNA miR-146a to suppress cigarette smoke-induced COX-2 protein expression in lung fibroblasts.

Author information

1
Department of Medicine, McGill University, 3626 St. Urbain Street, Montreal, Quebec H2X 2P2, Canada.
2
Research Institute of the McGill University Health Centre, McGill University, 3626 St. Urbain Street, Montreal, Quebec H2X 2P2, Canada.
3
Department of Medicine, McGill University, 3626 St. Urbain Street, Montreal, Quebec H2X 2P2, Canada; Research Institute of the McGill University Health Centre, McGill University, 3626 St. Urbain Street, Montreal, Quebec H2X 2P2, Canada.
4
Department of Medicine, McGill University, 3626 St. Urbain Street, Montreal, Quebec H2X 2P2, Canada; Research Institute of the McGill University Health Centre, McGill University, 3626 St. Urbain Street, Montreal, Quebec H2X 2P2, Canada. Electronic address: Carolyn.baglole@McGill.ca.

Abstract

Diseases due to cigarette smoke exposure, including chronic obstructive pulmonary disease (COPD) and lung cancer, are associated with chronic inflammation typified by the increased expression of cyclooxygenase-2 (COX-2) protein. RelB is an NF-κB family member that suppresses cigarette smoke induction of COX-2 through an unknown mechanism. The ability of RelB to regulate COX-2 expression may be via miR-146a, a miRNA that attenuates COX-2 in lung fibroblasts. In this study we tested whether RelB attenuation of cigarette smoke-induced COX-2 protein is due to miR-146a. Utilizing pulmonary fibroblasts deficient in RelB expression, together with siRNA knock-down of RelB, we show the essential role of RelB in diminishing smoke-induced COX-2 protein expression despite robust activation of the canonical NF-κB pathway and subsequent induction of Cox-2 mRNA. RelB did not regulate COX-2 protein expression at the level of mRNA stability. Basal levels of miR-146a were significantly lower in Relb-deficient cells and cigarette smoke increased miR-146a expression only in Relb-expressing cells. Inhibition of miR-146a had no effects on Relb expression or induction of Cox-2 mRNA by cigarette smoke but significantly increased COX-2 protein. These data highlight the potential of a RelB-miR-146a axis as a novel regulatory pathway that attenuates inflammation in response to respiratory toxicants.

KEYWORDS:

Chronic obstructive pulmonary disease; Cigarette smoke; Cyclooxygenase-2; Fibroblast; MicroRNA; NF-κB

PMID:
24472607
DOI:
10.1016/j.toxlet.2014.01.020
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center