Inhibition of Endoplasmic Reticulum Stress Alleviates Lung Injury Induced by Brain Death

Overview

Journal Inflammation

Specialties Allergy & Immunology
Pathology

Date 2017 Jul 29

PMID 28752363

Citations 4

Authors

Hongwei Tang

Jiakai Zhang

Shengli Cao

Bing Yan

Hongbo Fang

Huapeng Zhang

Wenzhi Guo

Shuijun Zhang

Affiliations

Soon will be listed here.

Abstract

Brain death (BD) can induce inflammation and injury of organs. Endoplasmic reticulum (ER) stress is associated with a variety of diseases. However, little is known about how ER stress is implicated in brain death (BD)-induced lung injury. In this study, a stable BD rat model was constructed to investigate the role of ER stress on BD-induced lung injury. H&E staining demonstrated that BD can induce lung injury in rats. The results of Western blot and immunohistochemistry showed that apoptosis was observed in the lung tissues of BD rats. And the level of GRP78, p-PERK, p-eIF2α, CHOP, and Caspase-12 was highly expressed in BD rats compared with the control group. Inhibition of ER stress with salubrinal reduced the BD-induced lung inflammation. Moreover, BD-induced increase of NF-κB activity was lowered by inhibition of ER stress. These results suggested that inhibition of ER stress alleviates BD-induced lung inflammation by regulating NF-κB signaling pathway.

Citing Articles

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References

Cao S, Yan B, Lu Y, Zhang G, Li J, Guo W . C/EBP homologous protein-mediated endoplasmic reticulum stress-related renal apoptosis is involved in rats with brain death. Transplant Proc. 2015; 47(2):354-8. DOI: 10.1016/j.transproceed.2014.10.012. View

Schmidt D, Textor B, Pein O, Licht A, Andrecht S, Sator-Schmitt M . Critical role for NF-kappaB-induced JunB in VEGF regulation and tumor angiogenesis. EMBO J. 2007; 26(3):710-9. PMC: 1794395. DOI: 10.1038/sj.emboj.7601539. View

Avlonitis V, Fisher A, Kirby J, Dark J . Pulmonary transplantation: the role of brain death in donor lung injury. Transplantation. 2003; 75(12):1928-33. DOI: 10.1097/01.TP.0000066351.87480.9E. View

Zhang K, Kaufman R . From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008; 454(7203):455-62. PMC: 2727659. DOI: 10.1038/nature07203. View

Engin F, Hotamisligil G . Restoring endoplasmic reticulum function by chemical chaperones: an emerging therapeutic approach for metabolic diseases. Diabetes Obes Metab. 2010; 12 Suppl 2:108-15. DOI: 10.1111/j.1463-1326.2010.01282.x. View

Avlonitis V, Wigfield C, Kirby J, Dark J . The hemodynamic mechanisms of lung injury and systemic inflammatory response following brain death in the transplant donor. Am J Transplant. 2005; 5(4 Pt 1):684-93. DOI: 10.1111/j.1600-6143.2005.00755.x. View

Cahill C, Zhu W, Oziolor E, Yang Y, Tam B, Rajanala S . Differential Expression of the Activator Protein 1 Transcription Factor Regulates Interleukin-1ß Induction of Interleukin 6 in the Developing Enterocyte. PLoS One. 2016; 11(1):e0145184. PMC: 4723075. DOI: 10.1371/journal.pone.0145184. View

Doyle K, Kennedy D, Gorman A, Gupta S, Healy S, Samali A . Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders. J Cell Mol Med. 2011; 15(10):2025-39. PMC: 4394214. DOI: 10.1111/j.1582-4934.2011.01374.x. View

Zweers N, Petersen A, van der Hoeven J, de Haan A, Ploeg R, de Leij L . Donor brain death aggravates chronic rejection after lung transplantation in rats. Transplantation. 2004; 78(9):1251-8. DOI: 10.1097/01.tp.0000142679.45418.96. View

10.

Zhang S, Cao S, Wang T, Yan B, Lu Y, Zhao Y . Modified brain death model for rats. Exp Clin Transplant. 2014; 12(5):469-73. DOI: 10.6002/ect.2013.0229. View

11.

Boyce M, Bryant K, Jousse C, Long K, Harding H, Scheuner D . A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science. 2005; 307(5711):935-9. DOI: 10.1126/science.1101902. View

12.

Hotamisligil G . Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010; 140(6):900-17. PMC: 2887297. DOI: 10.1016/j.cell.2010.02.034. View

13.

Baldwin Jr A . The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996; 14:649-83. DOI: 10.1146/annurev.immunol.14.1.649. View

14.

Cnop M, Foufelle F, Velloso L . Endoplasmic reticulum stress, obesity and diabetes. Trends Mol Med. 2011; 18(1):59-68. DOI: 10.1016/j.molmed.2011.07.010. View

15.

Kotloff R, Thabut G . Lung transplantation. Am J Respir Crit Care Med. 2011; 184(2):159-71. DOI: 10.1164/rccm.201101-0134CI. View

16.

Wang T, Zhang S, Cao S, Guo W, Yan B, Fang H . Protective effects of salubrinal on liver injury in rat models of brain death. Chin Med J (Engl). 2015; 128(11):1523-8. PMC: 4733771. DOI: 10.4103/0366-6999.157684. View

17.

Ron D, Walter P . Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007; 8(7):519-29. DOI: 10.1038/nrm2199. View

18.

Libermann T, Baltimore D . Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. Mol Cell Biol. 1990; 10(5):2327-34. PMC: 360580. DOI: 10.1128/mcb.10.5.2327-2334.1990. View

19.

Hosoi T, Ozawa K . Endoplasmic reticulum stress in disease: mechanisms and therapeutic opportunities. Clin Sci (Lond). 2009; 118(1):19-29. DOI: 10.1042/CS20080680. View

20.

Fang H, Zhang S, Guo W, Cao S, Yan B, Lu Y . Cobalt protoporphyrin protects the liver against apoptosis in rats of brain death. Clin Res Hepatol Gastroenterol. 2015; 39(4):475-81. DOI: 10.1016/j.clinre.2014.11.003. View