Cooperative and distinct functions of MK2 and MK3 in the regulation of the macrophage transcriptional response to lipopolysaccharide

Scientific Reports
Christian EhltingJohannes Georg Bode

Abstract

The p38MAPK downstream targets MAPKAP kinases (MK) 2 and 3 are critical for the regulation of the macrophage response to LPS. The extents to which these two kinases act cooperatively and distinctly in regulating LPS-induced inflammatory cytokine expression are still unclear. To address this uncertainty, whole transcriptome analyses were performed using bone marrow-derived macrophages (BMDM) generated from MK2-/- or MK2/3-/- animals and their wild-type littermates. The results suggest that in BMDM, MK2 and MK3 not only cooperatively regulate the transcript expression of signaling intermediates, including IL-10, IL-19, CXCL2 and the IL-4 receptor (IL-4R)α subunit, they also exert distinct regulatory effects on the expression of specific transcripts. Based on the differential regulation of gene expression by MK2 and MK3, at least six regulatory patterns were identified. Importantly, we confirmed our previous finding, which showed that in the absence of MK2, MK3 negatively regulates IFN-β. Moreover, this genome-wide analysis identified the regulation of Cr1A, NOD1 and Serpina3f as similar to that of IFN-β. In the absence of MK2, MK3 also delayed the nuclear translocation of NFκB by delaying the ubiquitination and subsequent degrada...Continue Reading

References

Nov 13, 1999·Nature Cell Biology·A KotlyarovM Gaestel
May 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elmer Y ChangGenhong Cheng
Feb 8, 2008·The Journal of Biological Chemistry·Georg StoecklinPaul Anderson
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Natalia RonkinaMatthias Gaestel
Jun 23, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Barbara SchaljoPavel Kovarik
Nov 13, 2010·Nucleic Acids Research·Andreas R GruberIvo L Hofacker
Dec 22, 2011·Molecular Systems Biology·Franz KratochvillPavel Kovarik
Feb 15, 2012·Cellular Signalling·Johannes G BodeDieter Häussinger
Mar 27, 2013·Molecular and Cellular Biology·Mei-Ling LiGary Brewer
May 29, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tim SmallieAndrew R Clark
May 26, 2016·Nucleic Acids Research·Christopher TiedjeMatthias Gaestel

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