https://doi.org/10.4081/ejh.2021.3292
Swertianolin ameliorates immune dysfunction in sepsis via blocking the immunosuppressive function of myeloid-derived suppressor cells
Submitted: 21 June 2021
Accepted: 26 July 2021
Published: 1 September 2021
Accepted: 26 July 2021
Abstract Views: 941
PDF: 660
HTML: 19
HTML: 19
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
In this study, we studied the long-term proliferation trajectory of myeloid-derived suppressor cells (MDSCs) in murine sepsis model and investigated whether swertianolin could modulate the immunosuppressive function of MDSCs. A murine sepsis model was established by cecal ligation and perforation (CLP), according to the Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS) guidelines. The bone marrow and spleen of the mice were collected at 24 h, 72 h, 7 and 15 d after sepsis induction. The proportions of monocytic-MDSCs (M-MDSCs; CD11b+LY6G-LY6Chi) and granulocytic-MDSCs (G-MDSC, CD11b+ Ly6G+ Ly6Clow) were analyzed by flow cytometry. Then, we have investigated whether swertianolin could modulate the immunosuppressive function of MDSCs in in vitro experiments. G-MDSCs and M-MDSCs increased acutely after sepsis with high levels sustained over a long period of time. G-MDSCs were the main subtype identified in the murine model of sepsis with polymicrobial peritonitis. Furthermore, it was found that swertianolin reduced significantly interleukin-10 (IL-10), nitric oxide (NO), reactive oxygen species (ROS), and arginase production in MDSCs, while reducing MDSC proliferation and promoting MDSC differentiation into dendritic cells. Swertianolin also improved T-cell activity by blocking the immunosuppressive effect of MDSCs. Both subsets of MDSCs significantly increased in the bone marrow and spleen of the mice with sepsis, with G-MDSCs being the main subtype identified. Swertianolin effectively regulated the functions of MDSCs and reduced immune suppression.
Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, et al. Developing a new definition and assessing new clinical criteria for septic shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:775-87.
DOI: https://doi.org/10.1001/jama.2016.0289
Lewis AJ, Rosengart MR. Bench-to-bedside: A translational perspective on murine models of sepsis. Surg Infect (Larchmt) 2018;19:137-41.
DOI: https://doi.org/10.1089/sur.2017.308
Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 2011;306:2594-605.
DOI: https://doi.org/10.1001/jama.2011.1829
Rosenthal MD. Persistent inflammatory, immunosuppressed, catabolic syndrome (PICS): A new phenotype of multiple organ failure. J Adv Nutr Hum Metab 2015;1:e784.
McPeak MB, Youssef D, Williams DA, Pritchett CL, Yao ZQ, McCall CE, et al. Frontline Science: Myeloid cell-specific deletion of Cebpb decreases sepsis-induced immunosuppression in mice. J Leukoc Biol 2017;102:191-200.
DOI: https://doi.org/10.1189/jlb.4HI1216-537R
Hotchkiss RSD, Monneret GP, Payen DM. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infect Dis 2013;13:260-8.
DOI: https://doi.org/10.1016/S1473-3099(13)70001-X
Bosurgi R. Sepsis: a need for new solutions. Lancet Infect Dis 2015;15:498-99.
DOI: https://doi.org/10.1016/S1473-3099(15)70030-7
Arens C, Bajwa SA, Koch C, Siegler BH, Schneck E, Hecker A, et al. Sepsis-induced long-term immune paralysis-results of a descriptive, explorative study. Crit Care 2016;20:93-9.
DOI: https://doi.org/10.1186/s13054-016-1233-5
Fleming V, Hu X, Weber R, Nagibin V, Groth C, Altevogt P, et al. Targeting myeloid-derived suppressor cells to bypass tumor-induced immunosuppression. Front Immunol 2018;9:398.
DOI: https://doi.org/10.3389/fimmu.2018.00398
Brudecki L, Ferguson DA, Yin D, Lesage GD, McCall CE, El Gazzar M. Hematopoietic Stem-progenitor cells restore immunoreactivity and improve survival in late sepsis. Infect Immun 2012;80:602-11.
Nagaraj S, Gabrilovich DI. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009;9:162-74.
Zeng Q, Yang B, Sun H, Feng G, Jin L, Zou Z, et al. Myeloid-derived suppressor cells are associated with viral persistence and downregulation of TCR ζ chain expression on CD8+ T cells in chronic hepatitis C patients. Mol Cells 2014;37:66-73.
DOI: https://doi.org/10.14348/molcells.2014.2282
Movahedi K, Guilliams M, Van den Bossche J, Van den Bergh R, Gysemans C, Beschin A, et al. Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 2008;111:4233-44.
DOI: https://doi.org/10.1182/blood-2007-07-099226
Uhel F, Azzaoui I, Gregoire M, Pangault C, Dulong J, Tadie JM, et al. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis. Am J Respir Crit Care Med 2017;196:315-27.
DOI: https://doi.org/10.1164/rccm.201606-1143OC
Nagaraj S, Youn J, Weber H, Iclozan C, Lu L, Cotter MJ, et al. Anti-inflammatory triterpenoid blocks immune suppressive function of MDSCs and improves immune response in cancer. Clin Cancer Res 2010;16:1812-23.
DOI: https://doi.org/10.1158/1078-0432.CCR-09-3272
Qu P, Wang L, Lin PC. Expansion and functions of myeloid-derived suppressor cells in the tumor microenvironment. Cancer Lett 2015;380:253-6.
DOI: https://doi.org/10.1016/j.canlet.2015.10.022
Veglia F, Perego M, Gabrilovich D. Myeloid-derived suppressor cells coming of age. Nat Immunol 2018;19:108-19.
DOI: https://doi.org/10.1038/s41590-017-0022-x
Wu X, Gu Y, Li L. The anti-hyperplasia, anti-oxidative and anti-inflammatory properties of Qing Ye Dan and swertiamarin in testosterone-induced benign prostatic hyperplasia in rats. Toxicol Lett 2017;265:9-16.
DOI: https://doi.org/10.1016/j.toxlet.2016.11.011
Zhang L, Cheng Y, Du X, Chen S, Feng X, Gao Y, et al. Swertianlarin, an herbal agent derived from Swertia mussotii Franch, attenuates liver injury, inflammation, and cholestasis in common bile duct-ligated rats. Evid Based Complement Alternat Med 2015;2015:948376.
DOI: https://doi.org/10.1155/2015/948376
Tang H, Ke Y, Ren Z, Lei X, Xiao S, Bao T, et al. Bioinformatics analysis of differentially expressed genes in hepatocellular carcinoma cells exposed to Swertiamarin. J Cancer 2019;10:6526-34.
DOI: https://doi.org/10.7150/jca.33666
He J, Tian C, Ouyang H, Adelakun TA, Yu B, Chang Y, et al. Determination of swertianolin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study. Biomed Chromatogr 2014;28:1418-22.
DOI: https://doi.org/10.1002/bmc.3184
Tian C, Zhang T, Wang L, Shan Q, Jiang L. The hepatoprotective effect and chemical constituents of total iridoids and xanthones extracted from Swertia mussotii Franch. J Ethnopharmacol 2014;154:259-66.
DOI: https://doi.org/10.1016/j.jep.2014.04.018
Wani BA, Ramamoorthy D, Rather MA, Arumugam N, Qazi AK, Majeed R, et al. Induction of apoptosis in human pancreatic MiaPaCa-2 cells through the loss of mitochondrial membrane potential (DeltaPsim) by Gentiana kurroo root extract and LC-ESI-MS analysis of its principal constituents. Phytomedicine 2013;20:723-33.
DOI: https://doi.org/10.1016/j.phymed.2013.01.011
Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009;9:162-74.
DOI: https://doi.org/10.1038/nri2506
Bronte V. Myeloid-derived suppressor cells in inflammation: Uncovering cell subsets with enhanced immunosuppressive functions. Eur J Immunol 2009;39:2670-2.
DOI: https://doi.org/10.1002/eji.200939892
Condamine T, Gabrilovich DI. Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function. Trends Immunol 2010;32:19-25.
DOI: https://doi.org/10.1016/j.it.2010.10.002
Cao T, Geng C, Ma Y, He K, Zhou N, Zhou J, et al. Chemical constituents of Swertia delavayi and their anti-hepatitis B virus activity. Zhongguo Zhong Yao Za Zhi 2015;40:897-902.
Hotchkiss RS, Moldawer LL, Phimister EG. Parallels between cancer and infectious disease. N Engl J Med 2014;371:380-3.
DOI: https://doi.org/10.1056/NEJMcibr1404664
Ward PA, Rittirsch D, Flierl MA, Huber-Lang MS. Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc 2008;4:31-6.
DOI: https://doi.org/10.1038/nprot.2008.214
Nascimento DC, Melo PH, Piñeros AR, Ferreira RG, Colón DF, Donate PB, et al. IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population. Nat Commun 2017;8:389-95.
DOI: https://doi.org/10.1038/ncomms14919
Janols H, Bergenfelz C, Allaoui R, Larsson A, Rydén L, Björnsson S, et al. A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in gram-positive cases. J Leukoc Biol 2014;96:685-93.
DOI: https://doi.org/10.1189/jlb.5HI0214-074R
Richard S. Hotchkiss MD. The pathophysiology and treatment of sepsis. N Engl J Med 2003;11:273-8.
Riviello ED, Sugira V, Twagirumugabe T. Sepsis research and the poorest of the poor. Lanvet Infect Dis 2015;15:501-3.
DOI: https://doi.org/10.1016/S1473-3099(15)70148-9
Rosenthal MD, Moore FA. Persistent inflammation, immunosuppression, and catabolism: Evolution of multiple organ dysfunction. Surg Infect 2016;17:167-72.
DOI: https://doi.org/10.1089/sur.2015.184
Benjamim CF. Reversal of long-term sepsis-induced immunosuppression by dendritic cells. Blood 2005;1:127-31.
DOI: https://doi.org/10.1182/blood-2004-08-3251
Deutschman CS, Tracey KJ. Sepsis: Current dogma and new perspectives. Immunity 2014;40:463-75.
DOI: https://doi.org/10.1016/j.immuni.2014.04.001
Delano MJ, Ward PA. Sepsis-induced immune dysfunction: can immune therapies reduce mortality? J Clin Invest 2016;126:23-31.
DOI: https://doi.org/10.1172/JCI82224
Shao R, Fang Y, Yu H, Zhao L, Jiang Z, Li CS. Monocyte programmed death ligand-1 expression after 3-4 days of sepsis is associated with risk stratification and mortality in septic patients: a prospective cohort study. Crit Care 2016;20:124.
DOI: https://doi.org/10.1186/s13054-016-1301-x
Goodwin AJ, Rice DA, Simpson KN, Ford DW. Frequency, cost, and risk factors of readmissions among severe sepsis survivors. Crit Care Med 2015;43:738-46.
DOI: https://doi.org/10.1097/CCM.0000000000000859
Lv R, Zhao J, Lei M, Xiao D, Yu Y, Xie J. IL-33 Attenuates sepsis by inhibiting IL-17 receptor signaling through upregulation of SOCS3. Cell Physiol Biochem 2017;42:1961-72.
DOI: https://doi.org/10.1159/000479836
Mira JC, Gentile LF, Mathias BJ, Efron PA, Brakenridge SC, Mohr AM, et al. Sepsis pathophysiology, chronic critical illness, and persistent inflammation-immunosuppression and catabolism syndrome. Crit Care Med 2017;45:253-62.
DOI: https://doi.org/10.1097/CCM.0000000000002074
Brudecki L, Ferguson DA, Yin D, Lesage GD, McCall CE, El Gazzar M. Hematopoietic stem-progenitor cells restore immunoreactivity and improve survival in late sepsis. Infect Immun 2012;80:602-11.
DOI: https://doi.org/10.1128/IAI.05480-11
How to Cite
Ren, Z., Tang, H., Wan, L., Liu, X., Tang, N., Wang, L., & Guo, Z. (2021). Swertianolin ameliorates immune dysfunction in sepsis <em>via</em> blocking the immunosuppressive function of myeloid-derived suppressor cells . European Journal of Histochemistry, 65(3). https://doi.org/10.4081/ejh.2021.3292
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- H. Valpotić, A. Kovšca Janjatović, G. Lacković, F. Božić, V. Dobranić, D. Svoboda, I. Valpotić, M. Popović, Increased number of intestinal villous M cells in levamisole - pretreated weaned pigs experimentally infected with F4ac+ enterotoxigenic Escherichia coli strain , European Journal of Histochemistry: Vol. 54 No. 2 (2010)
- Sabrina Giacoppo, Agnese Gugliandolo, Oriana Trubiani, Federica Pollastro, Gianpaolo Grassi, Placido Bramanti, Emanuela Mazzon, Cannabinoid CB2 receptors are involved in the protection of RAW264.7 macrophages against the oxidative stress: an in vitro study , European Journal of Histochemistry: Vol. 61 No. 1 (2017)
- Y. Dong, C. Yang, Z. Wang, Z. Qin, J. Cao, Y. Chen, The injury of serotonin on intestinal epithelium cell renewal of weaned diarrhoea mice , European Journal of Histochemistry: Vol. 60 No. 4 (2016)
- Xiong Bing Li, Jia Li Li, Chao Wang, Yong Zhang, Jing Li, Identification of mechanism of the oncogenic role of FGFR1 in papillary thyroid carcinoma , European Journal of Histochemistry: Vol. 68 No. 3 (2024)
- I. Kopera, M. Durlej, A. Hejmej, K. Knapczyk-Stwora, M. Duda, M. Slomczynska, M. Koziorowski, B. Bilinska, Effects of pre- and postnatal exposure to flutamide on connexin 43 expression in testes and ovaries of prepubertal pigs , European Journal of Histochemistry: Vol. 54 No. 2 (2010)
- Qiong Lin, Tianxing Yu, Xiaohua Li, Xin Lin, Yong Fan, Liyu Xu, Umbilical cord mesenchymal stem cells inhibited inflammation of bronchial epithelial cells by regulating Hedgehog pathway , European Journal of Histochemistry: Vol. 67 No. 4 (2023)
- Christian Zuppinger, George Gibbons, Priyanka Dutta-Passecker, Adrian Segiser, Henriette Most, Thomas M. Suter, Characterization of cytoskeleton features and maturation status of cultured human iPSC-derived cardiomyocytes , European Journal of Histochemistry: Vol. 61 No. 2 (2017)
- C. Bai, D. Wang, C. Li, D. Jin, C. Li, W. Guan, Y. Ma, Establishment and biological characteristics of a Jingning chicken embryonic fibroblast bank , European Journal of Histochemistry: Vol. 55 No. 1 (2011)
- Kazuhiko Hashimoto, Yutaka Oda, Koichi Nakagawa, Terumasa Ikeda, Kazuhiro Ohtani, Masao Akagi, LOX-1 deficient mice show resistance to zymosan-induced arthritis , European Journal of Histochemistry: Vol. 62 No. 1 (2018)
- Bo Dai, Hailin Liu, Dingmin Juan, Kaize Wu, Ruhao Cao, The role of miRNA-29b1 on the hypoxia-induced apoptosis in mammalian cardiomyocytes , European Journal of Histochemistry: Vol. 68 No. 3 (2024)
<< < 4 5 6 7 8 9 10 11 12 13 > >>
You may also start an advanced similarity search for this article.
