Involvement of ATF3 in the negative regulation of iNOS expression and NO production in activated macrophages

Immunologic Research
Da Hye JungS Pyo

Abstract

Macrophage-associated nitric oxide (NO) production plays a crucial role in the pathogenesis of tissue damage. However, negative factors that regulate NO production remains poorly understood despite its significance of NO homeostasis. Here, we show that activating transcription factor 3 (ATF3), a transcriptional regulator of cellular stress responses, was strongly induced in activated macrophages and its depletion resulted in pronounced enhancement of inducible nitric oxide synthase (iNOS) gene expression and subsequently the induction of high levels of NO production. In response to lipopolysaccharide (LPS) and IFN-γ, ATF3 inhibited transcriptional activity of NF-κB by interacting with the N-terminal (1-200 amino acids) of p65 and was bound to the NF-κB promoter, leading to suppression of iNOS gene expression. In addition, inhibitory effects of ATF3 on iNOS and NO secretion were suppressed by inhibitor of casein kinase II (CK2) activity or its knockdown. Moreover, the levels of ATF3 were highly elevated in established cecal ligation and puncture or LPS-injected mice, a model of endotoxemia. ATF3 is also elevated in peritoneal macrophages. Collectively, our findings suggest that ATF3 regulates NO homeostasis by associating with N...Continue Reading

References

Jan 1, 1997·Annual Review of Immunology·J MacMickingC Nathan
Mar 11, 2000·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·K M Rao
Feb 22, 2001·The Journal of Clinical Investigation·G SassG Tiegs
Sep 29, 2001·Nature Immunology·C Bogdan
Jun 3, 2004·Life Sciences·Fugen Aktan
Jul 23, 2004·Physiological Reviews·Fabio L M RicciardoloGert Folkerts
May 26, 2005·Pharmacological Reviews·Vincenzo MollaceDaniela Salvemini
Jan 24, 2006·Bioscience, Biotechnology, and Biochemistry·Hiroaki KajiItaru Yamamoto
Sep 20, 2006·Molecular Immunology·Ciera H KhuuSteven L Weinstein
Oct 4, 2006·The Biochemical Journal·Dan LuTsonwin Hai
Aug 26, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Matthew R ThompsonBryan R G Williams
Oct 7, 2009·The Journal of Clinical Investigation·Kent DoiRobert A Star
Dec 19, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryosuke TakiiAkira Nakai
Nov 3, 2010·Scandinavian Journal of Immunology·T Qidwai, F Jamal
May 10, 2011·Free Radical Biology & Medicine·Antonio Martínez-RuizSantiago Lamas
Dec 21, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kyeongjin KimSung Hee Um
Mar 5, 2013·Archives of Biochemistry and Biophysics·Cecilia Chavarría, José M Souza
Aug 8, 2013·The Journal of Clinical Investigation·Chris C WolfordTsonwin Hai

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Citations

Dec 7, 2016·Molecular and Cellular Biology·Kenneth T FarabaughMaria Hatzoglou
Dec 29, 2020·Frontiers in Immunology·Sandy R LarsonLaurel L Lenz
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eleanor L AtkinsonDavid R Spring
Apr 10, 2019·Journal of Medicinal Chemistry·Hao GuoFrank J Dekker

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