Acquisition of anergy to proinflammatory cytokines in nonimmune cells through endoplasmic reticulum stress response: a mechanism for subsidence of inflammation

The Journal of Immunology : Official Journal of the American Association of Immunologists
Kunihiro HayakawaMasanori Kitamura

Abstract

Acute endoplasmic reticulum (ER) stress causes induction of inflammatory molecules via activation of NF-kappaB. However, we found that, under ER stress conditions, renal mesangial cells acquire anergy to proinflammatory stimuli. Priming of the cells with ER stress inducers (tunicamycin, thapsigargin, A23187, and AB5 subtilase cytotoxin) caused blunted induction of MCP-1 in response to TNF-alpha, IL-1beta, macrophage-derived factors, or bystander macrophages. The magnitude of suppression was closely correlated with the level of GRP78, an endogenous indicator of ER stress. The suppression of MCP-1 under ER stress conditions was reversible and observed in general regardless of cell types or triggers of ER stress. The decrease in the level of MCP-1 mRNA was ascribed to transcriptional suppression via unexpected inhibition of NF-kappaB, but not to accelerated mRNA degradation. Subsequent experiments revealed that TNFR-associated factor 2, an essential component for TNF-alpha signaling, was down-regulated by ER stress. We also found that, under ER stress conditions, expression of NF-kappaB suppressor A20 was induced. Overexpression of A20 resulted in suppression of cytokine-triggered NF-kappaB activation and knockdown of A20 by RNA i...Continue Reading

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Citations

May 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shuqi DuMasanori Kitamura
Aug 22, 2009·Journal of the American Society of Nephrology : JASN·Masanori Kitamura
Sep 28, 2010·Toxins·Adrienne W Paton, James C Paton
Dec 15, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yang ZhaoMasanori Kitamura
Sep 19, 2014·Nature Immunology·Sophie JanssensBart N Lambrecht
May 24, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yun WangQing Jiang
Oct 3, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Masanori Kitamura
Feb 5, 2010·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Masanori Kitamura, Nobuhiko Hiramatsu
Dec 5, 2013·American Journal of Respiratory Cell and Molecular Biology·Lokesh MakhijaAnurag Agrawal
Jan 18, 2011·International Reviews of Immunology·Masanori Kitamura
Jan 18, 2011·The Journal of Biological Chemistry·Sriram RavindranAnne George
Jun 30, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hiroaki YamazakiMasanori Kitamura
Jun 26, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daisuke HaramaAtsuhito Nakao
May 8, 2010·Peritoneal Dialysis International : Journal of the International Society for Peritoneal Dialysis·Ryouji OgataMasanori Kitamura
Oct 31, 2009·Journal of the American Society of Nephrology : JASN·Kunihiro HayakawaMasanori Kitamura
Jun 6, 2009·Journal of Cellular Biochemistry·Tao HuangJian Yao
Apr 10, 2016·Journal of Digestive Diseases·Jian Sheng WuQin Fen Chen
Apr 5, 2013·Seminars in Immunopathology·Masanori Kitamura
May 22, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shotaro NakajimaMasanori Kitamura
Feb 4, 2009·Antioxidants & Redox Signaling·Masanori Kitamura
Aug 3, 2021·Ageing Research Reviews·Md Sahab UddinLee Wei Lim
Jul 6, 2010·Biochemical Pharmacology·Lynn VerstrepenRudi Beyaert

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