Divergent intracellular pathways regulate interleukin-1β-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells

Perry, Mark M.; Williams, Andrew E.; Tsitsiou, Eleni; Larner-Svensson, Hanna M.; Lindsay, Mark A.

doi:10.1016/j.febslet.2009.09.038

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Volume 583, Issue 20 , Pages 3349-3355, 20 October 2009

Divergent intracellular pathways regulate interleukin-1β-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells

Edited by Lukas Huber

Mark M. Perry
- Airways Disease, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK
Andrew E. Williams
- Airways Disease, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK
Eleni Tsitsiou
- NIHR Translational Research Facility in Respiratory Medicine, University of Manchester, 2nd Floor, Education and Research Centre, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LY, UK
Hanna M. Larner-Svensson
- Airways Disease, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK
Mark A. Lindsay
- NIHR Translational Research Facility in Respiratory Medicine, University of Manchester, 2nd Floor, Education and Research Centre, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LY, UK
- Corresponding author. Address: 2nd Floor, Education and Research Centre, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LY, UK. Fax: +44 161 291 5873.

Received 19 August 2009; received in revised form 21 September 2009; accepted 23 September 2009. published online 29 September 2009.

Abstract

We have previously reported that IL-β-induced miR-146a and miR-146b expression negatively regulates IL-8 and RANTES release in human alveolar A549 epithelial cells. To determine the intracellular pathways that regulate this response, we demonstrate IL-1β-induced activation of the nuclear factor (NF)-κB, extracellular regulated kinase (ERK)-1/2, c-jun N-terminal kinase (JNK)-1/2 and p38 mitogen activated kinase (MAP) kinase pathways. Subsequent pharmacological studies show that IL-1β-induced miR-146a, IL-8 and RANTES production was regulated via NF-κB and JNK-1/2 whilst miR-146b expression was mediated via MEK-1/2 and JNK-1/2. These divergent intracellular pathways likely explain the differential expression and biological action of the miR-146 isoforms.

Keywords: MicroRNA, Inflammation, Epithelium, Innate immune response, Interleukin-1β, miR-146