The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway.

The Journal of Biological Chemistry
R M VabulasH Schild

Abstract

The heat shock protein Gp96 has been shown to induce specific immune responses. On one hand, this phenomenon is based on the specific interaction with CD91 that mediates endocytosis and results in major histocompatibility complex class I-restricted representation of the Gp96-associated peptides. On the other hand, Gp96 induces activation of professional antigen-presenting cells, resulting in the production of pro-inflammatory cytokines and up-regulation of costimulatory molecules by unknown mechanisms. In this study, we have analyzed the consequences of Gp96 interaction with cells expressing different Toll-like receptors (TLRs) and with bone marrow-derived dendritic cells from mice lacking functional TLR2 and/or TLR4 molecules. We find that the Gp96-TLR2/4 interaction results in activation of nuclear factor kappaB-driven reporter genes and mitogen- and stress-activated protein kinases and induces IkappaBalpha degradation. Bone marrow-derived dendritic cells of C3H/HeJ and more pronounced C3H/HeJ/TLR2(-/-) mice fail to respond to Gp96. Interestingly, activation of bone marrow-derived dendritic cells depends on endocytosis of Gp96 molecules. Our results provide, for the first time, the molecular basis for understanding the Gp96-m...Continue Reading

References

Oct 1, 1991·Current Opinion in Immunology·P K Srivastava
Nov 1, 1993·Journal of Immunotherapy with Emphasis on Tumor Immunology : Official Journal of the Society for Biological Therapy·N E BlachereP K Srivastava
Feb 27, 1999·Current Opinion in Immunology·H SchildH G Rammensee
Jan 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·K OhashiH Kolb
Jul 6, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M HirschfeldJ J Weis
Aug 15, 2000·European Journal of Immunology·H Singh-JasujaH Schild
Aug 30, 2000·Nature·A Aderem, R J Ulevitch
Dec 29, 2000·Nature·H HemmiS Akira
Mar 15, 2001·Nature Immunology·R J BinderP K Srivastava
Mar 29, 2001·Nature Immunology·D T Golenbock, M J Fenton
Mar 30, 2001·The Journal of Biological Chemistry·B BerwinC V Nicchitta
Apr 5, 2001·Trends in Immunology·T Kaisho, S Akira
May 24, 2001·Immunity·H Wagner
Sep 8, 2001·Nature Immunology·M SchnareR Medzhitov
Dec 12, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·H ZhengZ Li

❮ Previous
Next ❯

Citations

Jul 21, 2005·Cancer Immunology, Immunotherapy : CII·John G FacciponteJohn R Subjeck
May 12, 2005·Cancer Immunology, Immunotherapy : CII·Yi ZengEmmanuel Katsanis
Dec 21, 2004·Springer Seminars in Immunopathology·Kenneth L RockYan Shi
Jul 20, 2007·Medical Microbiology and Immunology·Anke Osterloh, Minka Breloer
Sep 2, 2011·Cardiovascular Drugs and Therapy·Magomed Khaidakov, Jawahar L Mehta
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Rajagopal N AravalliJames R Lokensgard
Jul 19, 2012·Current Infectious Disease Reports·John H Boyd
Oct 16, 2009·Neuromolecular Medicine·Jacob A SloaneTimothy Vartanian
Oct 30, 2008·Cell Stress & Chaperones·Brian Henderson, Samantha Henderson
Dec 2, 2010·Cell Stress & Chaperones·Elisa TramentozziPaola Finotti
Jan 30, 2004·Cytokine & Growth Factor Reviews·Simone MocellinMario Lise
Oct 14, 2003·Microbes and Infection·Cécile M C FremondValérie F J Quesniaux
Apr 17, 2003·Developmental and Comparative Immunology·Jacques Robert
Dec 24, 2002·Current Opinion in Immunology·Christopher C Norbury, Luis J Sigal
Dec 24, 2002·Current Opinion in Immunology·Julie C Baker-LePainChristopher V Nicchitta
Dec 24, 2002·Trends in Immunology·Geoffrey B JohnsonJeffrey L Platt
Oct 9, 2013·Immunology and Cell Biology·Monica Escamilla-TilchErnesto Antonio Vázquez-Sánchez
Nov 3, 2011·Nature Communications·Sudesh Pawaria, Robert J Binder
Dec 5, 2008·Nature Reviews. Cancer·Seth Rakoff-Nahoum, Ruslan Medzhitov
Mar 15, 2008·Nature Reviews. Immunology·Hajime Kono, Kenneth L Rock
Feb 4, 2003·Nature Reviews. Molecular Cell Biology·Jürg TschoppKimberly Burns
Feb 21, 2008·Molecular & Cellular Proteomics : MCP·Om V SinghPamela L Zeitlin
Dec 4, 2002·The Journal of Experimental Medicine·Julie C Baker-LePainChristopher V Nicchitta
Feb 20, 2003·The Journal of Experimental Medicine·Iris CaramalhoJocelyne Demengeot
Oct 22, 2003·The Journal of Experimental Medicine·Mathias W HornefStaffan Normark
May 9, 2006·Antioxidants & Redox Signaling·Peter A Jordan, Jonathan M Gibbins
Feb 23, 2011·Antioxidants & Redox Signaling·Jingjun LuJawahar L Mehta
Feb 8, 2008·International Immunology·Anke OsterlohMinka Breloer
Oct 11, 2011·Rheumatology·Fui G Goh, Kim S Midwood
Jun 18, 2004·Current Opinion in Rheumatology·Reinhart SeiblSteffen Gay
Jul 4, 2006·Plastic and Reconstructive Surgery·Yang-Sung LeeAtsushi Yamada
Feb 13, 2007·Current Opinion in Nephrology and Hypertension·Christopher Y LuJianlin Chen
Sep 2, 2011·Current Opinion in Lipidology·Anna M Lundberg, Zhong-qun Yan
Mar 8, 2006·Immunology and Cell Biology·Masoud H ManjiliJohn R Subjeck
Jun 23, 2006·Infection and Immunity·Brian HendersonAnthony R M Coates
Jul 9, 2008·Biochemistry. Biokhimii︠a︡·S Rakoff-Nahoum, R Medzhitov
Nov 17, 2010·Biochemistry. Biokhimii︠a︡·A I TukhvatulinA L Gintsburg
Nov 28, 2007·Annual Review of Pathology·Kenneth L Rock, Hajime Kono
Mar 1, 2013·Thrombosis and Haemostasis·F CarboneF Montecucco

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.