Journal
TOXICOLOGY LETTERS
Volume 226, Issue 2, Pages 107-116Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2014.01.020
Keywords
MicroRNA; Cyclooxygenase-2; NF-kappa B; Cigarette smoke; Fibroblast; Chronic obstructive pulmonary disease
Categories
Funding
- Canada Foundation for Innovation
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Canadian Institutes for Health Research (CIHR)
- Fonds de recherche du Quebec-Sante (FRQ-S)
- Meakins-Christie Post-Doctoral Fellowship Award
Ask authors/readers for more resources
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-kappa B 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-kappa B 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 Re1B-miR-146a axis as a novel regulatory pathway that attenuates inflammation in response to respiratory toxicants. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available