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Front. Immunol. | doi: 10.3389/fimmu.2018.02906

Long non-coding RNAs are central regulators of the IL-1b-induced inflammatory response in normal and idiopathic pulmonary lung fibroblasts

Marina Hadjicharalambous1,  Benoit T. Roux1,  Carol Feghali-Bostwick2, Lynne A. Murray3, Deborah L. Clarke4 and  Mark A. Lindsay1*
  • 1University of Bath, United Kingdom
  • 2Medical University of South Carolina, United States
  • 3AstraZeneca (Sweden), Sweden
  • 4Boehringer Ingelheim (United Kingdom), United Kingdom

There is accumulating evidence to indicate that long non-coding RNAs (lncRNAs) are important regulators of the inflammatory response. In this report, we have employed next generation sequencing to identify 14 lncRNAs that are differentially expressed in human lung fibroblasts following the induction of inflammation using interleukin-1b (IL-1b). Knockdown of the two most highly expressed lncRNAs, IL7AS and MIR3142HG, showed that IL7AS negatively regulated IL-6 release whilst MIR3142HG was a positive regulator of IL-8 and CCL2 release. Parallel studies in fibroblasts derived from patients with idiopathic pulmonary fibrosis showed similar increases in IL7AS levels, that also negatively regulate IL-6 release. In contrast, IL-1b-induced MIR3142HG expression and its metabolism to miR-146a, was reduced by 4- and 9-fold in IPF fibroblasts, respectively. This correlated with a reduced expression of inflammatory mediators whilst MIR3142HG knockdown showed no effect upon IL-8 and CCL2 release. Pharmacological studies showed that IL-1b-induced IL7AS and MIR3142 production and release of IL-6, IL-8 and CCL2 in both control and IPF fibroblasts were mediated via an NF-kB-mediated pathway. In summary, we have catalogued those lncRNAs that are differentially expressed following IL-1-activation of human lung fibroblasts, shown that IL7AS and MIR3142HG regulate the inflammatory response and demonstrated that the reduced inflammatory response in IPF fibroblast is correlated with attenuated expression of MIR3142HG/miR-146a.

Keywords: long non-coding RNA, fibroblast, Idiopathic Pulmonary Fibrosis, Interleukin-1 (IL-1β), Inflammation

Received: 31 Jul 2018; Accepted: 27 Nov 2018.

Edited by:

Miriam Wittmann, University of Leeds, United Kingdom

Reviewed by:

Ka Man Law, University of California, Los Angeles, United States
James F. Burrows, Queen's University Belfast, United Kingdom  

Copyright: © 2018 Hadjicharalambous, Roux, Feghali-Bostwick, Murray, Clarke and Lindsay. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Mark A. Lindsay, University of Bath, Bath, BA2 7AY, United Kingdom, m.a.lindsay@bath.ac.uk