Vasoactive Intestinal Peptide Ameliorates Renal Injury in a Pristane-induced Lupus Mouse Model by Modulating Th17/Treg Balance

Overview

Journal BMC Nephrol

Publisher Biomed Central

Specialty Nephrology

Date 2019 Sep 7

PMID 31488076

Citations 9

Authors

Dongdong Fu

Soulixay Senouthai

Junjie Wang

Yanwu You

Affiliations

Soon will be listed here.

Abstract

Background: Lupus nephritis (LN) is an inflammation of the kidneys and is a major cause of mortality in systemic lupus erythaematosus (SLE) patients. In addition, Th17/Treg balance is one of the most important factors that can promote the development of LN. It has been reported that vasoactive intestinal peptide (VIP) is associated with the downregulation of both inflammatory and autoimmune diseases through regulating T lymphocyte balance. Therefore, the aim of this study was to determine the role of VIP in modulating Th17/Treg balance in LN.

Methods: LN was induced in BALB/c female mice by injection pristane. After 3 months, mice were randomly divided into four groups: control, VIP + control, LN and VIP + LN. Autoantibody levels were tested by ELISA. The distribution of Th17/Treg cells in vivo and in vitro was detected by FC. Renal tissues were examined by PASM and DIF for pathology and Foxp3CD3. The mRNA and protein expression levels of pro- and anti-inflammatory cytokines were detected by qRT-PCR and western blotting.

Results: VIP can improve renal injury by regulating Th17/Treg imbalance in LN mice. Proteinuria, renal function defects and autoantibodies were significantly decreased, and Th17/Treg cell balance was restored in VIP compared with LN mice. In addition, VIP improved renal lesions by promoting the expression of Foxp3CD3 in renal tissue. Furthermore, VIP downregulated the mRNA and protein expression of IL-17, IL-6 and upregulated Foxp3, IL-10 expression.

Conclusions: VIP reduced LN proteinuria and renal function defects and restored the Th17/Treg cell balance. Furthermore, VIP also downregulated autoantibody and inflammatory cytokine expression and upregulated Foxp3 and IL-10 expression.

Citing Articles

The roles of adenosine signaling in systemic lupus erythematosus.

Dong K, Wu X, Liu Y, Yang L, Liu C, Wang H Heliyon. 2024; 10(9):e29848.

PMID: 38699049 PMC: 11064148. DOI: 10.1016/j.heliyon.2024.e29848.

Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus.

Tsai Y, Liao P, Hsiao K, Wu H, Lin C, Yang K Front Immunol. 2023; 14:1230264.

PMID: 37771588 PMC: 10522836. DOI: 10.3389/fimmu.2023.1230264.

Asiaticoside ameliorates renal ischemia/reperfusion injury by promoting CD4CD25FOXP3 treg cell differentiation.

Tang S, Xie X, Wang M, Wei W Heliyon. 2023; 9(7):e17390.

PMID: 37539103 PMC: 10395025. DOI: 10.1016/j.heliyon.2023.e17390.

Lactobacillus plantarum CQPC02 intervenes in mouse lupus nephritis by regulating the NF-κB signaling pathway.

Wu Y, Zou X, Zhao X, Ma X, Yao X, Wen Y Braz J Microbiol. 2023; 54(3):2093-2102.

PMID: 37526890 PMC: 10485216. DOI: 10.1007/s42770-023-01072-5.

Research on the mechanism of prednisone in the treatment of ITP via VIP/PACAP-mediated intestinal immune dysfunction.

Yan X, Zhang Y, Lang H, Huang Z, Chen X, He H Eur J Med Res. 2023; 28(1):67.

PMID: 36750876 PMC: 9906942. DOI: 10.1186/s40001-023-00987-x.

References

Satoh M, Reeves W . Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane. J Exp Med. 1994; 180(6):2341-6. PMC: 2191761. DOI: 10.1084/jem.180.6.2341. View

Crispin J, Liossis S, Kis-Toth K, Lieberman L, Kyttaris V, Juang Y . Pathogenesis of human systemic lupus erythematosus: recent advances. Trends Mol Med. 2010; 16(2):47-57. PMC: 2823952. DOI: 10.1016/j.molmed.2009.12.005. View

Tan Y, Abad C, Wang Y, Lopez R, Waschek J . VPAC2 (vasoactive intestinal peptide receptor type 2) receptor deficient mice develop exacerbated experimental autoimmune encephalomyelitis with increased Th1/Th17 and reduced Th2/Treg responses. Brain Behav Immun. 2014; 44:167-175. PMC: 4275378. DOI: 10.1016/j.bbi.2014.09.020. View

Gonzalez-Rey E, Fernandez-Martin A, Chorny A, Delgado M . Vasoactive intestinal peptide induces CD4+,CD25+ T regulatory cells with therapeutic effect in collagen-induced arthritis. Arthritis Rheum. 2006; 54(3):864-76. DOI: 10.1002/art.21652. View

Han S, Zhuang H, Xu Y, Lee P, Li Y, Wilson J . Maintenance of autoantibody production in pristane-induced murine lupus. Arthritis Res Ther. 2016; 17:384. PMC: 4718029. DOI: 10.1186/s13075-015-0886-9. View

Jayawardena D, Guzman G, Gill R, Alrefai W, Onyuksel H, Dudeja P . Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine. Am J Physiol Gastrointest Liver Physiol. 2017; 313(1):G16-G25. PMC: 5538834. DOI: 10.1152/ajpgi.00081.2017. View

You Y, Qin Y, Lin X, Yang F, Li J, Sooranna S . Methylprednisolone attenuates lipopolysaccharide-induced Fractalkine expression in kidney of Lupus-prone MRL/lpr mice through the NF-kappaB pathway. BMC Nephrol. 2015; 16:148. PMC: 4551515. DOI: 10.1186/s12882-015-0145-y. View

Kasacka I, Piotrowska Z, Janiuk I . Influence of renovascular hypertension on the distribution of vasoactive intestinal peptide in the stomach and heart of rats. Exp Biol Med (Maywood). 2015; 240(11):1402-7. PMC: 4935291. DOI: 10.1177/1535370215587533. View

Arbuckle M, McClain M, Rubertone M, Scofield R, Dennis G, James J . Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003; 349(16):1526-33. DOI: 10.1056/NEJMoa021933. View

10.

Maroz N, Segal M . Lupus nephritis and end-stage kidney disease. Am J Med Sci. 2013; 346(4):319-23. DOI: 10.1097/MAJ.0b013e31827f4ee3. View

11.

Freitas E, de Oliveira M, Monticielo O . Pristane-induced lupus: considerations on this experimental model. Clin Rheumatol. 2017; 36(11):2403-2414. DOI: 10.1007/s10067-017-3811-6. View

12.

Jayawardena D, Anbazhagan A, Guzman G, Dudeja P, Onyuksel H . Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease. Mol Pharm. 2017; 14(11):3698-3708. PMC: 6053281. DOI: 10.1021/acs.molpharmaceut.7b00452. View

13.

Ibrahim H, Barrow P, Foster N . VIP as a potential therapeutic agent in gram negative sepsis. Endocr Metab Immune Disord Drug Targets. 2012; 12(4):308-15. DOI: 10.2174/187153012803832611. View

14.

Xing Q, Wang B, Su H, Cui J, Li J . Elevated Th17 cells are accompanied by FoxP3+ Treg cells decrease in patients with lupus nephritis. Rheumatol Int. 2011; 32(4):949-58. DOI: 10.1007/s00296-010-1771-0. View

15.

Deng G, Jin L . The effects of vasoactive intestinal peptide in neurodegenerative disorders. Neurol Res. 2016; 39(1):65-72. DOI: 10.1080/01616412.2016.1250458. View

16.

Katsuyama T, Tsokos G, Moulton V . Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus. Front Immunol. 2018; 9:1088. PMC: 5967272. DOI: 10.3389/fimmu.2018.01088. View

17.

Li C, Zhu F, Wu B, Wang Y . Vasoactive Intestinal Peptide Protects Salivary Glands against Structural Injury and Secretory Dysfunction via IL-17A and AQP5 Regulation in a Model of Sjögren Syndrome. Neuroimmunomodulation. 2018; 24(6):300-309. DOI: 10.1159/000486859. View

18.

Yang J, Chu Y, Yang X, Gao D, Zhu L, Yang X . Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum. 2009; 60(5):1472-83. DOI: 10.1002/art.24499. View

19.

Forghani P, Petersen C, Waller E . Activation of VIP signaling enhances immunosuppressive effect of MDSCs on CMV-induced adaptive immunity. Oncotarget. 2017; 8(47):81873-81879. PMC: 5669855. DOI: 10.18632/oncotarget.20704. View

20.

Jimeno R, Gomariz R, Gutierrez-Canas I, Martinez C, Juarranz Y, Leceta J . New insights into the role of VIP on the ratio of T-cell subsets during the development of autoimmune diabetes. Immunol Cell Biol. 2010; 88(7):734-45. DOI: 10.1038/icb.2010.29. View