Aim To analyse the ability of mesenchymal stem cells (MSCs) to regulate interleukin 6 (IL-6) and transforming growth factor (TGF-β) expression in vitro under co-culture conditions in human systemic lupus erythematosus (SLE). Method This study used a post-test group design that used peripheral blood mononuclear cells (PBMCs) from SLE patients at Kariadi Hospital, Semarang, Indonesia, and MSCs from a human umbilical cord. The cells were divided into two groups. The control group of PBMCs was treated with a standard medium, and the treatment group was co-cultured with the MSCs at a 1:40 ratio. Following 24 h incubation, the levels of IL-6 and TGF-β released in the culture medium were measured using a specific ELISA assay. Results This study showed a significant decrease in IL-6 level (p< 0.05) and a significant increase in TGF-β level (p<0.001) following 24 h of co-culture incubation of human SLE PBMCs cells and MSCs. Conclusion The PBMCs-to-MSCs ratio of 1:40 can regulate the IL-6 and TGF-β levels in human SLE PBMCs.
Prockop A, Horwitz D, E. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;315–7.
2.
Tanaka T, Narazaki M, Kishimoto T. IL-6 in Inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;16295.
3.
Davis L, Hutcheson J, Mohan C. The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus. J Interf Cytokine Res. 2011;781–9.
4.
Mantel P, Kuipers H, Boyman O, Rhyner C, Ouaked N, Rückert B, et al. GATA3-driven Th2 responses inhibit TGF-β1-induced FOXP3 expression and the formation of regulatory T cells. PLoS Biol. 2007;2847–61.
5.
Chen W, Konkel J. TGF-β and “‘Adaptive’” Foxp 3+ regulatory T cells. J Mol Cell Biol. 2010;30–6.
6.
Wan Y, Flavell R. Yin-Yang" functions of transforming growth factor-β and T regulatory cells in immune regulation. Immunol Rev. 2007;199–213.
7.
Putra A, Ridwan F, Putridewi A, Kustiyah A, Wirastuti K, Sadyah N, et al. The role of tnf-α induced mscs on suppressive inflammation by increasing tgf-β and il-10. Open Access Maced J Med Sci. 2018;1779–83.
8.
Aksoy E, Taboubi S, Torres D, Delbauve S, Hachani A, Whitehead M, et al. The p110δ isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock. Nat Immunol. 2012;1045–54.
9.
Bernardo M, Fibbe W. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell. 2013;392–402.
10.
Kurte LCP, Bravo-Alegría M, Contreras J, R, Lamperti N, Tejedor E, et al. Mesenchymal stem cells generate a CD4+CD25+Foxp3 + regulatory T cell population during the differentiation process of Th1 and Th17 cells. Stem Cell Res Ther. 2013;65.
11.
Sanz I, Lee FH, Sanz. Nat Rev Rheumatol -B cells as therapeutic targets in SLE. Nat Rev Rheumatol. 2010;326–37.
12.
Moulton V, Suarez-Fueyo A, Meidan E, Li H, Mizui M, Tsokos G. Pathogenesis of human systemic lupus erythematosus: a cellular perspective. Trends Mol Med. 2017;615–35.
13.
Rodríguez-Rodríguez N, Rosetti F, Crispín J, Cells. Systemic Lupus Erythematosus: Basic, Applied and Clinical Aspects. 2016;113–9.
14.
Keating A. Mesenchymal stromal cells: New directions. Cell Stem Cell. 2012;709–16.
15.
Wang D, Zhang H, Liang J, Li X, Feng X, Wang H, et al. Allogeneic mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus: 4 years of experience. Cell Transplant. 2013;2267–77.
16.
Dominici M, Blanc K, Le, Mueller I, Slaper-Cortenbach I, Marini F, et al. Keating TRANSPARENCY DECLARATION Conflicts of interest: None to declare.
17.
Ikhsan R, Putra A, Munir D, Darlan D, Suntoko B, Retno A. Mesenchymal stem cells induce regulatory T-cell population in human SLE. Bangladesh J Med Sci. 2020;743–8.
18.
Duff M, Ritter T, Ceredig R, Griffi M. Mesenchymal stem cell eff ects on T-cell eff ector pathways. Stem Cell Res Ther. 2011;1–9.
19.
Talaat R, Mohamed S, Bassyouni I, Raouf A. Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: correlation with disease activity. Cytokine. 2015;146–53.
20.
Su D, Lu Z, Shen M, Li X, Sun L. Roles of proand anti-inflammatory cytokines in the pathogenesis of SLE. J Biomed Biotechnol. 2012;347141.
21.
Hofmann K, Clauder A, Manz R. Targeting B cells and plasma cells in autoimmune diseases. Front Immunol. 2018;835.
22.
Tackey E, Lipsky P, Illei G. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus. 2004;333–43.
23.
English K, Ryan J, Tobin L, Murphy M, Barry F, Mahon B. Cell contact, prostaglandin E2 and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25 High fork head box P3+ regulatory T cells. Clin Exp Immunol. 2009;149–60.
24.
Wang D, Feng X, Lu L, Konkel J, Zhang H, Chen Z, et al. A CD8 T cell/indoleamine 2,3-dioxygenase axis is required for mesenchymal stem cell suppression of human systemic lupus erythematosus. Arthritis Rheumatol. 2014;2234–45.
25.
Fan L, Hu C, Chen J, Cen P, Wang J, Li L. Interaction between mesenchymal stem cells and B-cells. Int J Mol Sci. 2016;650.
26.
Sasaki M, Honmou O. Mesenchymal Stem Cell. Cell Therapy Against Cerebral Stroke : Comprehensive Reviews for Translational Researcher and CLinical Trial 1st ed Japan. 2017;147–55.
27.
Miyake K, Akahoshi M, Nakashima H. Th subset balance in lupus nephritis. J Biomed Biotechnol. 2011;980286.
28.
Jorge A, Lu N, Zhang Y, Rai S, Choi H. Unchanging premature mortality trends in systemic lupus erythematosus: A general population-based study. Rheumatol (United Kingdom). 1999;337–44.
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