Skip to main content
SpringerLink
Log in

Cross Talk Between ER Stress, Oxidative Stress, and Inflammation in Health and Disease

  • Protocol
Stress Responses

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1292))

Abstract

In mammals, endoplasmic reticulum (ER) stress, oxidative stress, and inflammatory responses compose the major defense networks that help the cells adapt to and survive stress conditions caused by biochemical, physiological and pathological stimuli. However, chronic ER stress, oxidative stress, or inflammation have been found to be associated with the initiation and progression of a variety of human diseases in the modern world. Under many pathophysiologic conditions, ER stress response, oxidative stress, and inflammatory responses are integrated and amplified in specialized cell types to facilitate the progression of disease. In the past few decades, ER stress response, oxidative stress, and inflammation as well as their interactive relationships have been hot research topics in biomedicine. In this review, we summarize the recent advance in our understanding of the cross talk between ER stress response, oxidative stress, and inflammation in immunity and in inflammatory and metabolic diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kaufman RJ (1999) Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 13:1211–1233

    Article  CAS  PubMed  Google Scholar 

  2. Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8:519–529

    Article  CAS  PubMed  Google Scholar 

  3. Gething MJ, Sambrook J (1992) Protein folding in the cell. Nature 355:33–45

    Article  CAS  PubMed  Google Scholar 

  4. Voeltz GK, Rolls MM, Rapoport TA (2002) Structural organization of the endoplasmic reticulum. EMBO Rep 3:944–950

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K (2001) XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107:881–891

    Article  CAS  PubMed  Google Scholar 

  6. Lee AH, Iwakoshi NN, Glimcher LH (2003) XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 23:7448–7459

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Hollien J, Weissman JS (2006) Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science 313:104–107

    Article  CAS  PubMed  Google Scholar 

  8. Hollien J, Lin JH, Li H, Stevens N, Walter P, Weissman JS (2009) Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J Cell Biol 186:323–331

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Upton JP, Wang L, Han D, Wang ES, Huskey NE, Lim L, Truitt M, McManus MT, Ruggero D, Goga A, Papa FR, Oakes SA (2012) IRE1alpha cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2. Science 338:818–822

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Han D, Lerner AG, Vande Walle L, Upton JP, Xu W, Hagen A, Backes BJ, Oakes SA, Papa FR (2009) IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell 138:562–575

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Cho JA, Lee AH, Platzer B, Cross BC, Gardner BM, De Luca H, Luong P, Harding HP, Glimcher LH, Walter P, Fiebiger E, Ron D, Kagan JC, Lencer WI (2013) The unfolded protein response element IRE1alpha senses bacterial proteins invading the ER to activate RIG-I and innate immune signaling. Cell Host Microbe 13:558–569

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Osorio F, Tavernier SJ, Hoffmann E, Saeys Y, Martens L, Vetters J, Delrue I, De Rycke R, Parthoens E, Pouliot P, Iwawaki T, Janssens S, Lambrecht BN (2014) The unfolded-protein-response sensor IRE-1alpha regulates the function of CD8alpha+ dendritic cells. Nat Immunol 15:248–257

    Article  CAS  PubMed  Google Scholar 

  13. Benhamron S, Hadar R, Iwawaky T, So JS, Lee AH, Tirosh B (2014) Regulated IRE1-dependent decay participates in curtailing immunoglobulin secretion from plasma cells. Eur J Immunol 44:867–876

    Article  CAS  PubMed  Google Scholar 

  14. Iqbal J, Dai K, Seimon T, Jungreis R, Oyadomari M, Kuriakose G, Ron D, Tabas I, Hussain MM (2008) IRE1beta inhibits chylomicron production by selectively degrading MTP mRNA. Cell Metab 7:445–455

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. So JS, Hur KY, Tarrio M, Ruda V, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, Lichtman AH, Iwawaki T, Glimcher LH, Lee AH (2012) Silencing of lipid metabolism genes through IRE1alpha-mediated mRNA decay lowers plasma lipids in mice. Cell Metab 16:487–499

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Coelho DS, Cairrao F, Zeng X, Pires E, Coelho AV, Ron D, Ryoo HD, Domingos PM (2013) Xbp1-independent Ire1 signaling is required for photoreceptor differentiation and rhabdomere morphogenesis in Drosophila. Cell Rep 5:791–801

    Article  CAS  PubMed  Google Scholar 

  17. Harding HP, Zhang Y, Ron D (1999) Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397:271–274

    Article  CAS  PubMed  Google Scholar 

  18. Novoa I, Zeng H, Harding HP, Ron D (2001) Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J Cell Biol 153:1011–1022

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Ma Y, Hendershot LM (2003) Delineation of a negative feedback regulatory loop that controls protein translation during endoplasmic reticulum stress. J Biol Chem 278:34864–34873

    Article  CAS  PubMed  Google Scholar 

  20. Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, Brown MS, Goldstein JL (2000) ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell 6:1355–1364

    Article  CAS  PubMed  Google Scholar 

  21. Brown MS, Ye J, Rawson RB, Goldstein JL (2000) Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100:391–398

    Article  CAS  PubMed  Google Scholar 

  22. Okada T, Yoshida H, Akazawa R, Negishi M, Mori K (2002) Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response. Biochem J 366:585–594

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Yamamoto K, Sato T, Matsui T, Sato M, Okada T, Yoshida H, Harada A, Mori K (2007) Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1. Dev Cell 13:365–376

    Article  CAS  PubMed  Google Scholar 

  24. Zhang K, Kaufman RJ (2008) From endoplasmic-reticulum stress to the inflammatory response. Nature 454:455–462

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Qiu Q, Zheng Z, Chang L, Zhao YS, Tan C, Dandekar A, Zhang Z, Lin Z, Gui M, Li X, Zhang T, Kong Q, Li H, Chen S, Chen A, Kaufman RJ, Yang WL, Lin HK, Zhang D, Perlman H, Thorp E, Zhang K, Fang D (2013) Toll-like receptor-mediated IRE1alpha activation as a therapeutic target for inflammatory arthritis. EMBO J 32:2477–2490

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Tu BP, Weissman JS (2004) Oxidative protein folding in eukaryotes: mechanisms and consequences. J Cell Biol 164:341–346

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Tu BP, Weissman JS (2002) The FAD- and O(2)-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum. Mol Cell 10:983–994

    Article  CAS  PubMed  Google Scholar 

  28. Cuozzo JW, Kaiser CA (1999) Competition between glutathione and protein thiols for disulphide-bond formation. Nat Cell Biol 1:130–135

    Article  CAS  PubMed  Google Scholar 

  29. Li G, Mongillo M, Chin KT, Harding H, Ron D, Marks AR, Tabas I (2009) Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J Cell Biol 186:783–792

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Hetz C (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 13:89–102

    CAS  PubMed  Google Scholar 

  31. Szabadkai G, Bianchi K, Varnai P, De Stefani D, Wieckowski MR, Cavagna D, Nagy AI, Balla T, Rizzuto R (2006) Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol 175:901–911

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Verfaillie T, Rubio N, Garg AD, Bultynck G, Rizzuto R, Decuypere JP, Piette J, Linehan C, Gupta S, Samali A, Agostinis P (2012) PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ 19:1880–1891

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Laing S, Wang G, Briazova T, Zhang C, Wang A, Zheng Z, Gow A, Chen AF, Rajagopalan S, Chen LC, Sun Q, Zhang K (2010) Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues. Am J Physiol Cell Physiol 299:C736–C749

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Smith JA, Khan M, Magnani DD, Harms JS, Durward M, Radhakrishnan GK, Liu YP, Splitter GA (2013) Brucella induces an unfolded protein response via TcpB that supports intracellular replication in macrophages. PLoS Pathog 9:e1003785

    Article  PubMed Central  PubMed  Google Scholar 

  35. Campos MA, Rosinha GM, Almeida IC, Salgueiro XS, Jarvis BW, Splitter GA, Qureshi N, Bruna-Romero O, Gazzinelli RT, Oliveira SC (2004) Role of Toll-like receptor 4 in induction of cell-mediated immunity and resistance to Brucella abortus infection in mice. Infect Immun 72:176–186

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. de Almeida LA, Macedo GC, Marinho FA, Gomes MT, Corsetti PP, Silva AM, Cassataro J, Giambartolomei GH, Oliveira SC (2013) Toll-like receptor 6 plays an important role in host innate resistance to Brucella abortus infection in mice. Infect Immun 81:1654–1662

    Article  PubMed Central  PubMed  Google Scholar 

  37. Oliveira SC, de Oliveira FS, Macedo GC, de Almeida LA, Carvalho NB (2008) The role of innate immune receptors in the control of Brucella abortus infection: toll-like receptors and beyond. Microbes Infect 10:1005–1009

    Article  CAS  PubMed  Google Scholar 

  38. Zanetti M (2013) Cell-extrinsic effects of the tumor unfolded protein response on myeloid cells and T cells. Ann N Y Acad Sci 1284:6–11

    Article  CAS  PubMed  Google Scholar 

  39. Iwakoshi NN, Lee AH, Vallabhajosyula P, Otipoby KL, Rajewsky K, Glimcher LH (2003) Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat Immunol. 4:321–329

    Article  CAS  PubMed  Google Scholar 

  40. van Anken E, Orsi A, Sitia R (2014) A RIDDle solved: why an intact IRE1/XBP1 signaling relay is key for humoral immune responses. Eur J Immunol 44(3):641–645

    Article  PubMed  Google Scholar 

  41. Brunsing R, Omori SA, Weber F, Bicknell A, Friend L, Rickert R, Niwa M (2008) B- and T-cell development both involve activity of the unfolded protein response pathway. J Biol Chem 283:17954–17961

    Article  CAS  PubMed  Google Scholar 

  42. Kamimura D, Bevan MJ (2008) Endoplasmic reticulum stress regulator XBP-1 contributes to effector CD8+ T cell differentiation during acute infection. J Immunol 181:5433–5441

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Kemp KL, Lin Z, Zhao F, Gao B, Song J, Zhang K, Fang D (2013) The serine-threonine kinase inositol-requiring enzyme 1alpha (IRE1alpha) promotes IL-4 production in T helper cells. J Biol Chem 288:33272–33282

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Scheu S, Stetson DB, Reinhardt RL, Leber JH, Mohrs M, Locksley RM (2006) Activation of the integrated stress response during T helper cell differentiation. Nat Immunol 7:644–651

    Article  CAS  PubMed  Google Scholar 

  45. Zheng M, Zhang Q, Joe Y, Lee BH, Ryu do G, Kwon KB, Ryter SW, Chung HT (2013) Curcumin induces apoptotic cell death of activated human CD4+ T cells via increasing endoplasmic reticulum stress and mitochondrial dysfunction. Int Immunopharmacol 15:517–523

    Article  CAS  PubMed  Google Scholar 

  46. Gargalovic PS, Gharavi NM, Clark MJ, Pagnon J, Yang WP, He A, Truong A, Baruch-Oren T, Berliner JA, Kirchgessner TG, Lusis AJ (2006) The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler Thromb Vasc Biol 26:2490–2496

    Article  CAS  PubMed  Google Scholar 

  47. Pereira ER, Liao N, Neale GA, Hendershot LM (2010) Transcriptional and post-transcriptional regulation of proangiogenic factors by the unfolded protein response. PLoS One 5

    Google Scholar 

  48. Shenderov K, Riteau N, Yip R, Mayer-Barber KD, Oland S, Hieny S, Fitzgerald P, Oberst A, Dillon CP, Green DR, Cerundolo V, Sher A (2014) Cutting edge: Endoplasmic reticulum stress licenses macrophages to produce mature IL-1beta in response to TLR4 stimulation through a caspase-8- and TRIF-dependent pathway. J Immunol 192:2029–2033

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Martinon F, Chen X, Lee AH, Glimcher LH (2010) TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat Immunol 11:411–418

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Afrazi A, Branca MF, Sodhi CP, Good M, Yamaguchi Y, Egan CE, Lu P, Jia H, Shaffiey S, Lin J, Ma C, Vincent G, Prindle T Jr, Weyandt S, Neal MD, Ozolek JA, Wiersch J, Tschurtschenthaler M, Shiota C, Gittes GK, Billiar TR, Mollen K, Kaser A, Blumberg R, Hackam DJ (2014) Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts induces necrotizing enterocolitis. J Biol Chem 289:9584–9599

    Article  CAS  PubMed  Google Scholar 

  51. Kaser A, Adolph TE, Blumberg RS (2013) The unfolded protein response and gastrointestinal disease. Semin Immunopathol 35:307–319

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EE, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS (2008) XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134:743–756

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Glas J, Seiderer J, Czamara D, Pasciuto G, Diegelmann J, Wetzke M, Olszak T, Wolf C, Muller-Myhsok B, Balschun T, Achkar JP, Kamboh MI, Franke A, Duerr RH, Brand S (2012) PTGER4 expression-modulating polymorphisms in the 5p13.1 region predispose to Crohn’s disease and affect NF-kappaB and XBP1 binding sites. PLoS One 7:e52873

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445

    Article  CAS  PubMed  Google Scholar 

  55. Igoillo-Esteve M, Marselli L, Cunha DA, Ladriere L, Ortis F, Grieco FA, Dotta F, Weir GC, Marchetti P, Eizirik DL, Cnop M (2010) Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes. Diabetologia 53:1395–1405

    Article  CAS  PubMed  Google Scholar 

  56. O’Neill CM, Lu C, Corbin KL, Sharma PR, Dula SB, Carter JD, Ramadan JW, Xin W, Lee JK, Nunemaker CS (2013) Circulating levels of IL-1B+IL-6 cause ER stress and dysfunction in islets from prediabetic male mice. Endocrinology 154:3077–3088

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgement

This work was partially supported by National Institutes of Health (NIH) grants DK090313 and ES017829, and American Heart Association Grants 0635423Z and 09GRNT2280479 (to K.Z.).

Author information

Authors and Affiliations

  1. Department of Immunology and Microbiology, Karmanos Cancer Institute, Wayne State University School of Medicine, 3202 Scott Hall, 540 East Canfield, Detroit, MI, 48201, USA

    Aditya Dandekar & Kezhong Zhang

  2. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 3202 Scott Hall, 540 East Canfield, Detroit, MI, 48201, USA

    Roberto Mendez & Kezhong Zhang

  3. Tumor Microenvironment Program, Karmanos Cancer Institute, Wayne State University School of Medicine, 3202 Scott Hall, 540 East Canfield, Detroit, MI, 48201, USA

    Kezhong Zhang

Authors
  1. Aditya Dandekar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberto Mendez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kezhong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kezhong Zhang .

Editor information

Editors and Affiliations

  1. Wentworth Institute of Technology, Boston, Massachusetts, USA

    Christine M. Oslowski

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Dandekar, A., Mendez, R., Zhang, K. (2015). Cross Talk Between ER Stress, Oxidative Stress, and Inflammation in Health and Disease. In: Oslowski, C. (eds) Stress Responses. Methods in Molecular Biology, vol 1292. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2522-3_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2522-3_15

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2521-6

  • Online ISBN: 978-1-4939-2522-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation