Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta

Nature
Masahiro YamamotoShizuo Akira

Abstract

Toll-like receptors (TLRs) recognize microbial components and trigger the inflammatory and immune responses against pathogens. IkappaBzeta (also known as MAIL and INAP) is an ankyrin-repeat-containing nuclear protein that is highly homologous to the IkappaB family member Bcl-3 (refs 1-6). Transcription of IkappaBzeta is rapidly induced by stimulation with TLR ligands and interleukin-1 (IL-1). Here we show that IkappaBzeta is indispensable for the expression of a subset of genes activated in TLR/IL-1R signalling pathways. IkappaBzeta-deficient cells show severe impairment of IL-6 production in response to a variety of TLR ligands as well as IL-1, but not in response to tumour-necrosis factor-alpha. Endogenous IkappaBzeta specifically associates with the p50 subunit of NF-kappaB, and is recruited to the NF-kappaB binding site of the IL-6 promoter on stimulation. Moreover, NF-kappaB1/p50-deficient mice show responses to TLR/IL-1R ligands similar to those of IkappaBzeta-deficient mice. Endotoxin-induced expression of other genes such as Il12b and Csf2 is also abrogated in IkappaBzeta-deficient macrophages. Given that the lipopolysaccharide-induced transcription of IkappaBzeta occurs earlier than transcription of these genes, some T...Continue Reading

References

Feb 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S KinoshitaT Kishimoto
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·T MatsusakaS Akira
Jan 1, 1993·Advances in Immunology·S AkiraT Kishimoto
Nov 1, 2000·Proceedings of the National Academy of Sciences of the United States of America·S SanjabiS T Smale
Mar 30, 2001·The Journal of Biological Chemistry·H HarutaK Todokoro
Feb 28, 2002·Annual Review of Immunology·Charles A Janeway, Ruslan Medzhitov
Mar 16, 2002·Nature Immunology·Vladimir ToshchakovStefanie N Vogel
May 2, 2002·Cell·Sankar Ghosh, Michael Karin
Oct 2, 2002·Immunity·Sean DoyleGenhong Cheng
Jan 14, 2003·Annual Review of Immunology·Kiyoshi TakedaShizuo Akira
Feb 5, 2003·Biochemical and Biophysical Research Communications·Akiko EtoKoichiro Takeshige
Jul 4, 2003·The Journal of Biological Chemistry·Tatsuya SaitohShoji Yamaoka
Aug 7, 2003·Current Opinion in Pharmacology·Luke A J O'Neill
Oct 9, 2003·The EMBO Journal·Alexander HoffmannDavid Baltimore

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Citations

Jan 9, 2007·Inflammatory Bowel Diseases·Johan Van LimbergenJack Satsangi
Sep 29, 2009·Archives of Dermatological Research·Jessica Amber JenningsDale S Feldman
Mar 20, 2010·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·T UmenaiJ Imanishi
Jun 26, 2010·Japanese Journal of Ophthalmology·Shigeru Kinoshita, Mayumi Ueta
Dec 29, 2005·Journal of Clinical Immunology·Diana C Hargreaves, Ruslan Medzhitov
Oct 27, 2010·Cell Research·Hideaki KamataTomoichiro Asano
Jul 25, 2006·Nature Immunology·Masahiro YamamotoShizuo Akira
Oct 18, 2008·Nature Reviews. Immunology·Sankar Ghosh, Matthew S Hayden
Oct 28, 2009·Nature Reviews. Immunology·Ruslan Medzhitov, Tiffany Horng
Oct 31, 2006·Oncogene·A HoffmannG Ghosh
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Shumpei YamauchiAtsushi Miyajima
Oct 13, 2010·Proceedings of the National Academy of Sciences of the United States of America·Keisuke ObokiSusumu Nakae
Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Tohru MiyakeOsamu Takeuchi
Aug 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Qin YanYouhai H Chen
Oct 17, 2012·Proceedings of the National Academy of Sciences of the United States of America·Marzia RossatoFlavia Bazzoni
Sep 15, 2010·The Journal of Biological Chemistry·Takeshi IntoKen-ichiro Shibata
Feb 22, 2011·The Journal of Biological Chemistry·Søren Ulrik SønderUlrich Siebenlist
Jan 19, 2006·The Journal of Experimental Medicine·Junya MasumotoNaohiro Inohara
Aug 26, 2009·The Journal of Experimental Medicine·Akihiro KimuraTadamitsu Kishimoto
Oct 27, 2010·The Journal of Experimental Medicine·Melanie ScheibelRoland M Schmid
Jun 15, 2011·The Journal of Experimental Medicine·Masahiro YamamotoKiyoshi Takeda
Feb 9, 2012·The Journal of Experimental Medicine·Maria BuxadéCristina López-Rodríguez
Feb 28, 2009·International Immunology·Taro Kawai, Shizuo Akira
Aug 13, 2010·Eye & Contact Lens·Mayumi Ueta, Shigeru Kinoshita
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Andrea Oeckinghaus, Sankar Ghosh
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Fengyi Wan, Michael J Lenardo
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Tom Huxford, Gourisankar Ghosh
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Gioacchino Natoli
Feb 4, 2012·Genes & Development·Matthew S Hayden, Sankar Ghosh
Oct 14, 2004·Science's STKE : Signal Transduction Knowledge Environment·Paul W Bates, Shigeki Miyamoto

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