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Inhibition of Micro‐RNA 146a Expression in Lung Fibroblasts by Fluticasone Propionate, Salmeterol Xinafoate, and Related Agents
Author(s) -
Toews Myron,
Schulte Nancy,
Bang Jarrod,
Rennard Stephen,
Liu Xiangde
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.619.12
Subject(s) - adenylyl cyclase , fluticasone propionate , salmeterol , forskolin , chemistry , pharmacology , inflammation , dithiothreitol , receptor , medicine , biochemistry , enzyme , asthma
Micro‐RNA (miR) 146a is induced by inflammatory stimuli, and its pro‐inflammatory targets suggest that it may limit the inflammatory response. Fluticasone propionate (FP) and salmeterol xinafoate (SX) are used together to treat asthma, an inflammatory disease. Their effects on interleukin 1‐beta (IL‐1β)‐induced expression of miR‐146a by HFL‐1 lung fibroblasts were evaluated by quantitative RT‐PCR. Exposure of cells to the anti‐inflammatory steroid FP (1 nM) for 24 hr caused a nearly 70% inhibition. Two beta‐2 adrenergic receptor agonists, the long‐acting SX (10 nM) and the short‐acting albuterol (Alb, 10 μM) also inhibited miR‐146a expression, but only by 25‐35%. Prostaglandin E2 (100 nM) and the direct adenylyl cyclase activator forskolin (Fsk, 30 μM) both inhibited miR‐146a expression similarly to SX and Alb, suggesting cAMP elevation as the mechanism for these agents. Two primary isolates of human lung fibroblasts showed similar decreases in miR‐146a as for HFL‐1 cells when treated with FP, SX, or Fsk. FP has anti‐inflammatory effects in the airways that are augmented by concurrent SX, yet both FP and SX reduced fibroblast expression of anti‐inflammatory miR‐146a. Whether this is a direct effect of these agents or due to their overall inhibition of inflammation remains to be defined. Reduction in miR‐146a levels by these agents might limit their anti‐inflammatory actions, perhaps to prevent excess inhibition of inflammatory pathways. Supported by Glaxo Smith Kline Respiratory Division Investigator‐Initiated Grant 200164 .