IL10 in Lupus Nephritis
Detection and relationship with disease activity
Keywords:
systemic lupus erythematosus, IL10, lupus nephritisAbstract
Introduction: Glomerulonephritis is a major determinant of the course and prognosis of systemic lupus erythematosus (SLE) and is evident in 40%–85% of patients. IL10, a cytokine produced by monocytes and-to a lesser extent-lymphocytes, has pleiotropic effects in immune regulation and inflammation. It enhances B cell survival, proliferation, differentiation, and antibody production; these effects play a role in autoimmune diseases. Among identified polymorphisms in the IL10 promoter, three linked single nucleotide polymorphisms (SNPs) of -1082 G/A, 819 T/C, and -592 A/C have been shown to influence the IL10 gene expression. Compared with the -592 C allele, the 592 A is associated with lower IL10 production in vitro. The objectives of this study were to investigate the -592 A/C polymorphism in patients with and without lupus nephritis and to assess its influence on IL10 secretion in vivo and its role in pathogenesis and clinicopathological characteristics of lupus nephritis.
Methods: This case control study was conducted on 40 SLE patients recruited for the study from those attending the nephrology department of the Theodor Bilharz Research Institute (outpatient clinic and inpatient ward) in 2013. Patients were divided into two groups, group I (SLE patients without evidence of nephritis) and group II (SLE patients with lupus nephritis). Data were analyzed using SPSS (version 12), a t-test, Chi square, ANOVA, and the Pearson product–moment correlation coefficient.
Results: Our study found an increase in IL10 serum in lupus nephritis patients compared to those without renal involvement (without statistical significance). No significant differences emerged in the level of IL10 serum among different pathological classes.
Conclusion: The IL10 gene (-592 A/C) polymorphism, though not associated with lupus nephritis’s susceptibility in the present study, does play a role.
References
Bethunaickan R, Berthier CC, Zhang W, Kretzler M, Davidson A. Comparative transcriptional profiling of 3 murine models of SLE nephritis reveals both unique and shared regulatory networks. PLoS One. 2013;2013;8(10):e77489. doi: 10.1371/journal.pone.0077489. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Chong WP, Ip WK, Wong WH, Lau CS, Chan TM, Lau YL. Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus. Genes Immun. 2004;5:484–92. doi: 10.1038/sj.gene.6364119. [PubMed] [CrossRef] [Google Scholar]
Hammer M, Mages J, Dietrich H, Schmitz F, Striebel F, Murray PJ, et al. Control of dual-specificity phosphatase-1 expression in activated macrophages by IL-10. Eur J Immunol. 2005;35(10):2991–3001. doi: 10.1002/eji.200526192. [PubMed] [CrossRef] [Google Scholar]
Koenig KF, Kalbermatter SA, Menter T, Mayr M, Kiss D. Rapidly progressive lupus nephritis with extremely high levels of antineutrophil cytoplasmic antibodies. Case Rep Nephrol Urol. 2004;4:5–11. doi: 10.1159/000358557. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 2008;226(1):205–18. doi: 10.1111/j.1600-065X.2008.00706.x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Nakahara J, Maeda M, Aiso S, Suzuki N. Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy. Clin Rev Allergy Immunol. 2012;42( 1):26–34. doi: 10.1007/s12016-011-8287-6. [PubMed] [CrossRef] [Google Scholar]
Brennan FM, Green P, Amjadi P, Robertshaw HJ, Alvarez-Iglesias M, Takata M. Interleukin-10 regulates TNF-alpha-converting enzyme (TACE/ADAM-17) involving a TIMP-3 dependent and independent mechanism. Eur J Immunol. 2008;38(4):1106–17. doi: 10.1002/eji.200737821. [PubMed] [CrossRef] [Google Scholar]
Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010;10(3):170–81. doi: 10.1038/nri2711. [PubMed] [CrossRef] [Google Scholar]
Sharma A, Kumar M, Aich J, Hariharan M, Brahmachari SK, Agrawal A, et al. Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a. Proc Natl Acad Sci U S A. 2009;106(14):5761–6. doi: 10.1073/pnas.0808743106. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Li X, Mai J, Virtue A, Yin Y, Gong R, Sha X, Gutchigian S, Frisch A, Hodge I, Jiang X, Wang H, Yang XF, et al. IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines. PloS One. 2012;7( 3):e33628. doi: 10.1371/journal.pone.0033628. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Hedrich CM1, Crispin JC, Rauen T, Ioannidis C, Apostolidis SA, Lo MS, et al. cAMP response element modulator α controls IL2 and IL17A expression during CD4 lineage commitment and subset distribution in lupus. Proc Natl Acad Sci USA. 2012;109(41):16606–11. doi: 10.1073/pnas.1210129109. Epub 2012 Sep 26. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Zhang Y, Zhao M, Sawalha AH, Richardson B, Lu Q. Impaired DNA methylation and its mechanisms in CD4(+)T cells of systemic lupus erythematosus. J Autoimmun. 2013;41:92–99. doi: 10.1016/j.jaut.2013.01.005. [PubMed] [CrossRef] [Google Scholar]
Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, et al. Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nat Med. 2010;16( 4):452–9. doi: 10.1038/nm.2106. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Costa-Reis P, Sullivan KE. Genetics and epigenetics of systemic lupus erythematosus. Curr Rheumatol Rep. 2013;15(9):369. doi: 10.1007/s11926-013-0369-4. [PubMed] [CrossRef] [Google Scholar]
Nakahara J, Maeda M, Aiso S, Suzuki N. Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy. Clin Rev Allergy Immunol. 2012;42( 1):26–34. doi: 10.1007/s12016-011-8287-6. [PubMed] [CrossRef] [Google Scholar]
Sikka G, Miller KL, Steppan J, Pandey D, Jung SM, Fraser CD, et al. Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age. Exp Gerontol. 2013;48( 2):128–35. doi: 10.1016/j.exger.2012.11.001. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Schulte LN, Eulalio A, Mollenkopf HJ, Reinhardt R, Vogel J. Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family. EMBO J. 2011;30( 10):1977–89. doi: 10.1038/emboj.2011.94. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
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