Effects of simvastatin on the function of splenic CD4+ and CD8+ T cells in sepsis mice

Immunologic Research
Bing-Bing KongYu Wang

Abstract

Simvastatin may be beneficial for treating sepsis due to its immune-regulating properties, although the mechanisms remain elusive. Herein, we hypothesized simvastatin may attenuate T cell dysfunction induced by sepsis. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. Male C57BL/6 mice were pre-treated with simvastatin (0.2 μg/g of body weight) before CLP. The expression of B and T lymphocyte attenuator (BTLA) on splenic CD4+ T cells and T cell apoptosis, CD4+ and CD8+ T cells were quantified by flow cytometry. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. Formation of TNF-α and interleukin 10 (IL-10) in the spleen and plasma levels of presepsin, IL-1β, and IL-6 were determined using enzyme-linked immunosorbent assay. Simvastatin markedly inhibited the reduction in cytokine secretion from lipopolysaccharide (LPS)-stimulated splenocytes. Simvastatin-treated mice had significantly decreased the percentages of negative costimulatory receptor BTLA on CD4 T cell expression. Simvastatin markedly reduced T cell apoptosis through downregulating the Fas/FasL expression and decrease the percentage of caspase-3 activity in spleen tissue...Continue Reading

References

May 2, 1998·The EMBO Journal·C ScaffidiM E Peter
Aug 28, 1998·Science·G Evan, T Littlewood
Mar 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kate A FelmetJoseph A Carcillo
May 6, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Simon A JonesStefan Rose-John
Nov 1, 2005·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Yasunori YaegashiShigeatsu Endo
Apr 24, 2007·The Lancet Infectious Diseases·Marius TerblancheDaniel G Hackam
Sep 20, 2008·Nature Reviews. Immunology·Daniel RittirschPeter A Ward
Oct 24, 2008·Clinical and Vaccine Immunology : CVI·Anna SinistroAlberto Bergamini
Jan 10, 2009·Nature Protocols·Daniel RittirschPeter A Ward
Apr 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Xin HuangAlfred Ayala
May 12, 2009·Immunological Reviews·Guifang Cai, Gordon J Freeman
Jan 23, 2010·The Journal of Clinical Investigation·Jason W RoschElaine I Tuomanen
Mar 24, 2010·Annual Review of Immunology·Theresa L Murphy, Kenneth M Murphy
Jul 2, 2010·The New England Journal of Medicine·Richard S Hotchkiss, Steven Opal
Dec 15, 2010·Burns : Journal of the International Society for Burn Injuries·David C BeffaEdward A Carter
Feb 8, 2011·Biochimica Et Biophysica Acta·Jürgen SchellerStefan Rose-John
Mar 4, 2011·Shock·Shigeaki InoueRichard S Hotchkiss
Mar 23, 2011·Critical Care : the Official Journal of the Critical Care Forum·Caroline GuignantFabienne Venet
Mar 29, 2011·Vascular Pharmacology·Michael BergmanHanna Bessler
Oct 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guido AdlerThomas Jacobs
May 1, 2012·Pathologie-biologie·M Adib-Conquy, J-M Cavaillon
Aug 30, 2013·The New England Journal of Medicine·Derek C Angus, Tom van der Poll
Oct 15, 2013·Langenbeck's Archives of Surgery·Georg F Weber, Filip K Swirski
Dec 3, 2013·Critical Care : the Official Journal of the Critical Care Forum·Nicholas J ShubinAlfred Ayala
Jan 7, 2014·Critical Care : the Official Journal of the Critical Care Forum·Katherine ChangRichard Hotchkiss
Aug 25, 2015·Clinica Chimica Acta; International Journal of Clinical Chemistry·Ricardo CarpioGeorg Hess

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
density gradient centrifugation
enzyme-linked immunosorbent assay
PCR
ELISA
flow cytometry

Software Mentioned

Image Pro Plus
CellQuest
Elements
LineGene9600 Plus
NIS

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis