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Regulation of REGγ on LPS-mediated peritonitis(PDF)


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Regulation of REGγ on LPS-mediated peritonitis
Sun Jinxia1 Li Li1 Wang Rui2 and Huang Zhong1
1) Health Science Center, Shenzhen University, Shenzhen 518060, Guangdong Province, P.R.China
2) College of Pharmacy, Liaocheng University, Liaocheng 252059, Shandong Province, P.R.China
peritonitis proteasome adoptive transfer bone marrow chimera hematopoietic system enzyme-linked immunosorbent assay
R 392
Mouse peritonitis model is established by LPS peritoneal injection to analyze the roles of proteasome activator REGγ in LPS-mediated peritonitis. Bone marrow chimera mice are generated by adoptive transfer of bone marrow cells. Survival assay is used to research the effect of REGγ deficiency on survival rate. Expression of proinflammatory factors are detected via enzyme-linked immunosorbent assay (ELISA). As compared to the wild-type (WT) mice, the REGγ-knockout (KO) mice shows significantly lower survival rate and lower expression of the proinflammatory factors TNFα, IL-1β and MCP-1. Furthermore, bone marrow from WT and KO mice is isolated and transferred adoptively to X-ray irradiated WT mice to generate WTchimera and KOchimera bone marrow chimera mice. The results suggest that KOchimera mice also manifest obviously lower survival rate and proinflammatory factors expression of TNFα, IL-1β and MCP-1 after peritoneal injection of LPS to WTchimera and KOchimera. Thus, these data suggest that REGγ deficiency in inflammatory cells of hematopoietic origin accelerates LPS-mediated decline of survival rate and suppresses expression of proinflammatory factors TNFα, IL-1β and MCP-1.


[1] Bosmann M, Ward P A. The inflammatory response in sepsis[J]. Trends Immunol, 2013, 34: 129-136.
[2] Otto G P, Sossdorf M, Claus R A, et al. The late phase of sepsis is characterized by an increased icrobiological burden and death rate[J]. Critical Care, 2011, 15(4): R183.
[3] Cai Bolin, Deitch E A, Ulloa L. Novel insights for systemic inflammation in sepsis and hemorrhage[J]. Mediators of Inflammation, 2010,2010:642462.
[4] Thomas R C, Bath M F, Stover C M, et al. Exploring LPS-induced sepsis in rats and mice as a model to study potential protective effects of the nociceptin/orphanin FQ system[J]. Peptides, 2014, 61: 56-60.
[5] Rivera C A, Wheeler M D, Enomoto N, et al. A choline-rich diet improves survival in a rat model of endotoxin shock[J]. The American Journal of Physiology, 1998, 275(1): 862-867.
[6] Zhang Zhuo, Zhang Ruiwen. Proteasome activator PA28 gamma regulates p53 by enhancing its MDM2-mediated degradation[J]. The EMBO Journal, 2008, 27(6): 852-864.
[7] Dong Shuxian, Jia Caifeng, Zhang Shengping, et al. The REGγ proteasome regulates hepatic lipid metabolism through inhibition of autophagy[J]. Cell Metabolism, 2013, 18(3): 380-391.
[8] Li Shaungxi, Jiang Cong, Pan Jingjing, et al. Regulation of c-Myc protein stability by proteasome activator REGγ[J]. Cell Death and Differentiation, 2015, 22(6): 1000-1011.
[9] Sun Jinxia, Luan Yi, Xiang Dong, et al. The 11S proteasome subunit PSME3 is a positive feedforward regulator of NF-κB and important for host defense against bacterial pathogens[J]. Cell Reports, 2016, 14(4): 737-749.
[10] Xu Jinjin, Zhou Lei, Ji Lei, et al. The REGγ-proteasome forms a regulatory circuit with IκBε and NFκB in experimental colitis[J]. Nature Communications, 2016, 7: 10761.
[11] Sun Lianhui, Fan Guangjian, Shan Peipei, et al. Regulation of energy homeostasis by the ubiquitin-independent REGγ proteasome[J]. Nature Communications, 2016, 7: 12497.
[12] Boomer J S, Green J M, Hotchkiss R S. The changing immune system in sepsis Is individualized immuno-modulatory therapy the answer?[J]. Virulence, 2014, 5(1): 45-56.
[13] Opal S M, Fisher C J, Dhainaut J F, et al. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The interleukin-1 receptor antagonist sepsis investigator group[J]. Critical Care Medicine, 1997, 25(7): 1115-1124.
[14] Reinhart K, Menges T, Gardlund B, et al. Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: the RAMSES study[J]. Critical Care Medicine, 2001, 29(4): 765-769.
[15] Knaus W A, Harrell F E, Labrecque J F, et al. Use of predicted risk of mortality to evaluate the efficacy of anticytokine therapy in sepsis. The rhIL-1ra phase III sepsis syndrome study group[J]. Critical Care Medicine, 1996, 24(1): 46-56.
[16] Xiao Hongyan, Siddiqui J, Remick D G. Mechanisms of mortality in early and late sepsis[J]. Infection and Immunity, 2006, 74(9): 5227-5235.
[17] Huo Ruichao, Wang Lili, Wang Xiaoya, et al. Removal of regulatory T cells prevents secondary chronic infection but increases the mortality of subsequent sub-acute infection in sepsis mice[J]. Oncotarget, 2016, 7(10): 10962-10975.
[18] Hotchkiss R S, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy[J]. Nature Reviews Immunology, 2013, 13(12): 862-874.
[19] Luan Yingyi, Yao Yongming, Xiao Xianzhong, et al. Insights into the apoptotic death of immune cells in sepsis[J]. Journal of Interferon & Cytokine Research: the Official Journal of the International Society for Interferon and Cytokine Research, 2015, 35(1): 17-22.
[20] Chen Yuanli, Xu Guo, Liang Xiao, et al. Inhibition of hepatic cells pyroptosis attenuates CLP-induced acute liver injury[J]. American Journal of Translational Research, 2016, 8(12): 5685-5695.
[21] Shi Jianjin, Gao Wenqing, Shao Feng. Pyroptosis: Gasdermin-Mediated programmed necrotic cell death[J]. Trends in Biochemical Sciences, 2017, 42(4): 245-254.
[22] Jorgensen I, Miao E A. Pyroptotic cell death defends against intracellular pathogens[J]. Immunological Reviews, 2015, 265(1): 130-142.
[23] 孙锦霞,王瑞,黄钟. REGγ敲除对细胞浸润的抑制作用[J]. 深圳大学学报理工版,2017, 34(2):111-116.
Sun jinxia, Wang Rui, Huang Zhong. The inhibitory effect of REGγ-knockout on cell infiltration[J]. Journal of Shenzhen University Science and Engineering, 2017, 34(2): 111-116.(in Chinese)


Last Update: 2017-09-11