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 L-CP, 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 F-H, 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 n.d.
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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