Anti-inflammatory Effect of ApoE23 on -induced Sepsis in Mice

Overview

Journal Open Med (Wars)

Specialty General Medicine

Date 2023 Aug 3

PMID 37533741

Authors

Chuanqing Wang

Lijun Yin

Pan Fu

Guoping Lu

Xiaowen Zhai

Changsheng Yang

Affiliations

Soon will be listed here.

Abstract

Two independent experiments were performed with three groups each (sepsis control, sepsis, and sepsis with apoE23 treatment) to investigate the anti-inflammatory effect of apolipoprotein 23 (apoE23) in a mouse model of sepsis induced by . Survival rates; plasma level variations in tumor necrosis factor (TNF)-α, interleukin (IL)-6, and lipopolysaccharide (LPS); S. colony-forming units in the spleen tissue; and mRNA and protein expression levels of low-density lipoprotein receptor (LDLR), LDLR-related protein (LRP), syndecan-1, and scavenger receptor B1 were evaluated in the livers of mice from the three groups. Results found that the survival rate of septic mice treated with apoE23 was 100% within 48 h, while it was only 40% in septic mice without apoE23 treatment ( < 0.001). The plasma LPS, TNF-α, and IL-6 levels and the load in mice in the apoE23-treated group were significantly lower than those in septic mice ( < 0.05). Moreover, apoE23 restored the downregulated expression of LDLR and LRP in the liver tissue of septic mice. So apoE23 exhibits an anti-inflammatory effect in the mouse model of -induced sepsis. Further studies are required to understand the mechanisms underlying the anti-inflammatory effects of apoE23.

Citing Articles

Engineered endolysin of phage is a potent and broad-spectrum bactericidal agent against "ESKAPEE" pathogens.

Chen W, Han L, Chen X, Yi P, Li H, Ren Y Front Microbiol. 2024; 15:1397830.

PMID: 38784808 PMC: 11112412. DOI: 10.3389/fmicb.2024.1397830.

References

Guttman M, Prieto J, Handel T, Domaille P, Komives E . Structure of the minimal interface between ApoE and LRP. J Mol Biol. 2010; 398(2):306-19. PMC: 2880916. DOI: 10.1016/j.jmb.2010.03.022. View

Netea M, Joosten L, Keuter M, Wagener F, Stalenhoef A, van der Meer J . Circulating lipoproteins are a crucial component of host defense against invasive Salmonella typhimurium infection. PLoS One. 2009; 4(1):e4237. PMC: 2617780. DOI: 10.1371/journal.pone.0004237. View

Zhu Y, Kodvawala A, Hui D . Apolipoprotein E inhibits toll-like receptor (TLR)-3- and TLR-4-mediated macrophage activation through distinct mechanisms. Biochem J. 2010; 428(1):47-54. PMC: 3050041. DOI: 10.1042/BJ20100016. View

Yu H . HDL and Scavenger Receptor Class B Type I (SRBI). Adv Exp Med Biol. 2022; 1377:79-93. DOI: 10.1007/978-981-19-1592-5_6. View

Dos Santos C, Marshall J . Bridging lipid metabolism and innate host defense. Sci Transl Med. 2014; 6(258):258fs41. DOI: 10.1126/scitranslmed.3010501. View

Cao H, Huang W . HDL and Sepsis. Adv Exp Med Biol. 2022; 1377:129-139. DOI: 10.1007/978-981-19-1592-5_10. View

Dobson C, Sales S, Hoggard P, Wozniak M, Crutcher K . The receptor-binding region of human apolipoprotein E has direct anti-infective activity. J Infect Dis. 2006; 193(3):442-50. DOI: 10.1086/499280. View

Croy J, Brandon T, Komives E . Two apolipoprotein E mimetic peptides, ApoE(130-149) and ApoE(141-155)2, bind to LRP1. Biochemistry. 2004; 43(23):7328-35. DOI: 10.1021/bi036208p. View

Knodell R, Ishak K, Black W, Chen T, Craig R, Kaplowitz N . Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. 1981; 1(5):431-5. DOI: 10.1002/hep.1840010511. View

10.

Bhatia M, He M, Zhang H, Moochhala S . Sepsis as a model of SIRS. Front Biosci (Landmark Ed). 2009; 14(12):4703-11. DOI: 10.2741/3561. View

11.

Morris M, Gilliam E, Li L . Innate immune programing by endotoxin and its pathological consequences. Front Immunol. 2015; 5:680. PMC: 4285116. DOI: 10.3389/fimmu.2014.00680. View

12.

Strickland D, Au D, Cunfer P, Muratoglu S . Low-density lipoprotein receptor-related protein-1: role in the regulation of vascular integrity. Arterioscler Thromb Vasc Biol. 2014; 34(3):487-98. PMC: 4304649. DOI: 10.1161/ATVBAHA.113.301924. View

13.

Stanford K, Bishop J, Foley E, Gonzales J, Niesman I, Witztum J . Syndecan-1 is the primary heparan sulfate proteoglycan mediating hepatic clearance of triglyceride-rich lipoproteins in mice. J Clin Invest. 2009; 119(11):3236-45. PMC: 2769193. DOI: 10.1172/JCI38251. View

14.

Lee H, You D, Kim H, Sohn J, Kim M, Park J . Romo1-Derived Antimicrobial Peptide Is a New Antimicrobial Agent against Multidrug-Resistant Bacteria in a Murine Model of Sepsis. mBio. 2020; 11(2). PMC: 7157825. DOI: 10.1128/mBio.03258-19. View

15.

Howard G, Misra U, DeCamp D, Pizzo S . Altered interaction of Cis-dichlorodiammineplatinum(II)--modified alpha 2-macroglobulin (alpha 2M) with the low density lipoprotein receptor-related protein/alpha 2M receptor but not the alpha 2M signaling receptor. J Clin Invest. 1996; 97(5):1193-203. PMC: 507171. DOI: 10.1172/JCI118533. View

16.

Li L, Thompson P, Kitchens R . Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors. J Lipid Res. 2008; 49(8):1782-93. PMC: 2444006. DOI: 10.1194/jlr.M800172-JLR200. View

17.

Zhu X, Lei H, Wu J, Li J, Tang H, Wang Y . Systemic responses of BALB/c mice to Salmonella typhimurium infection. J Proteome Res. 2014; 13(10):4436-45. DOI: 10.1021/pr500770x. View

18.

Singer M, Deutschman C, Seymour C, Shankar-Hari M, Annane D, Bauer M . The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315(8):801-10. PMC: 4968574. DOI: 10.1001/jama.2016.0287. View

19.

van Oosten M, Rensen P, van Amersfoort E, van Eck M, van Dam A, Breve J . Apolipoprotein E protects against bacterial lipopolysaccharide-induced lethality. A new therapeutic approach to treat gram-negative sepsis. J Biol Chem. 2001; 276(12):8820-4. DOI: 10.1074/jbc.M009915200. View

20.

Levine D, Parker T, Donnelly T, Walsh A, RUBIN A . In vivo protection against endotoxin by plasma high density lipoprotein. Proc Natl Acad Sci U S A. 1993; 90(24):12040-4. PMC: 48121. DOI: 10.1073/pnas.90.24.12040. View