Abstract W P403: Interleukin-6 Is Regulated By Let7 In Ischemic Stroke
Background: Interleukin-6 (IL-6) is increased in ischemic stroke and associated with increased mortality and morbidity. microRNA are important regulators of inflammation and may be central to IL-6 expression in stroke. In this study we evaluated the regulation of IL-6 by microRNA in ischemic stroke.
Methods: IL-6 and microRNA were evaluated in circulating leukocytes of patients with ischemic stroke (n=106) and vascular risk factor controls (n=106). In a culture model of monocyte activation following stroke, the effect of let7 transfection on IL-6 expression was evaluated.
Results: In patients with ischemic stroke let7 microRNA was found to be decreased compared to risk factor controls (corrected p<0.01, fold change<1.4). This decrease correlated with an increase in IL-6 gene expression. In culture, stimulated monocytes expressed increased IL-6. Transfection of let7 mimic decreased IL-6 expression, whereas let7 inhibitor increased IL-6 expression. This effect was dependent on toll-like receptor 4 (TLR4) activation, and could be abolished with the TLR4 inhibitor Tak242.
Conclusions: Il-6 expression is regulated by microRNA let7 in ischemic stroke and thus may be an important determinant of post-ischemic cerebral inflammation.
Author Disclosures: G. Jickling: Research Grant; Significant; AHA-FTF. N. Shroff: None. B.P. Ander: None. D. Liu: None.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2015 by American Heart Association, Inc.