Temporal regulation of cytokine mRNA expression by tristetraprolin: dynamic control by p38 MAPK and MKP-1

American Journal of Physiology. Lung Cellular and Molecular Physiology
Pavan PrabhalaAlaina J Ammit

Abstract

Cytokines drive many inflammatory diseases, including asthma. Understanding the molecular mechanisms responsible for cytokine secretion will allow us to develop novel strategies to repress inflammation in the future. Harnessing the power of endogenous anti-inflammatory proteins is one such strategy. In this study, we investigate the p38 MAPK-mediated regulatory interaction of two anti-inflammatory proteins, mitogen-activated protein kinase phosphatase 1 (MKP-1) and tristetraprolin (TTP), in the context of asthmatic inflammation. Using primary cultures of airway smooth muscle cells in vitro, we explored the temporal regulation of IL-6 cytokine mRNA expression upon stimulation with TNF-α. Intriguingly, the temporal profile of mRNA expression was biphasic. This was not due to COX-2-derived prostanoid upregulation, increased expression of NLRP3 inflammasome components, or upregulation of the cognate receptor for TNF-α-TNFR1. Rather, the biphasic nature of TNF-α-induced IL-6 mRNA expression was regulated temporally by the RNA-destabilizing molecule, TTP. Importantly, TTP function is controlled by p38 MAPK, and our study reveals that its expression in airway smooth muscle cells is p38 MAPK-dependent and its anti-inflammatory activity...Continue Reading

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Citations

Dec 21, 2016·American Journal of Respiratory Cell and Molecular Biology·Brijeshkumar S PatelAlaina J Ammit
Mar 31, 2018·Cancer Medicine·Kathrin GärtnerReinhard Zeidler
Nov 11, 2017·Medical Oncology·Jian GuoJiazeng Xia
Mar 11, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Peta BradburyAlaina J Ammit
Oct 16, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Y S Prakash
Aug 12, 2017·Respiratory Research·Seyed M MoosaviAlaina J Ammit
Feb 9, 2017·Nucleic Acids Research·Kishan K NyatiTadamitsu Kishimoto
Sep 29, 2020·Frontiers in Immunology·Ishita ChoudharySonika Patial
Dec 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hiroaki TakemotoYoshinori Masuo

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