PMID: 15240733Jul 9, 2004Paper

Activated Ets2 is required for persistent inflammatory responses in the motheaten viable model

The Journal of Immunology : Official Journal of the American Association of Immunologists
G WeiM C Ostrowski

Abstract

The Ets2 transcription factor is constitutively phosphorylated on residue Thr(72) in macrophages derived from mice homozygous for the motheaten viable (me-v) allele of the hemopoietic cell phosphatase (Hcph) gene. To genetically test the importance of signaling through residue Thr(72) of Ets2 during inflammation, the Ets2(A72) mutant allele, which cannot be phosphorylated on Thr(72), was combined with the Hcph(me-v) allele in mice. Ets2(A72/A72) moderated the inflammation-related pathology of Hcph(me-v/me-v) mice, as demonstrated by the increased life span and the decreased macrophage infiltration in skin and lungs of these mice. Macrophage apoptosis induced by cytokine withdrawal was also increased in the double-mutant mice. Importantly, the Ets2(A72/A72) allele resulted in decreased expression of inflammatory response genes, including TNF-alpha, CCL3, matrix metalloprotease 9, integrin alpha(M), and Bcl-X in alveolar macrophage. Ets2 phosphorylation was required for persistent activation of TNF-alpha following LPS stimulation of bone marrow-derived macrophages. The phosphorylation of Ets2 functions in the severe inflammatory phenotype of the me-v model by mediating both macrophage survival and inflammatory gene expression.

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Citations

Sep 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ben A CrokerBruce Alan Beutler
Nov 22, 2013·The Journal of Biological Chemistry·Agnieszka BroniszSudarshana M Sharma
Jun 27, 2014·PloS One·Mohamed KabboutMichael C Ostrowski
Mar 24, 2020·Cellular & Molecular Immunology·Sarang TarteyThirumala-Devi Kanneganti
Oct 23, 2009·Nature·Anthony J TrimboliGustavo Leone
Jun 3, 2009·The Journal of Biological Chemistry·Zhongcheng ShiDekai Zhang
May 13, 2011·American Journal of Respiratory Cell and Molecular Biology·Christopher P BaranClay B Marsh
May 7, 2019·Frontiers in Immunology·Graziella CurtaleMassimo Locati
Oct 24, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Fang YaoXiaochun Bai
May 24, 2006·The Journal of Biological Chemistry·Stephen S LinThomas M Roberts
Aug 16, 2006·Oncogene·D-M WangJ S Lipsick
Jun 14, 2017·Journal of Leukocyte Biology·Clare L Abram, Clifford A Lowell
Apr 4, 2007·Molecular and Cellular Biology·Rong HuMichael C Ostrowski
Dec 14, 2004·The Journal of Biological Chemistry·Su Wol ChungMark A Perrella
Sep 26, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Yanjun HouMichael C Ostrowski

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