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.
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. p. 2267–77.
2.
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. p. 337–44.
3.
Miyake K, Akahoshi M, Nakashima H. Th subset balance in lupus nephritis. J Biomed Biotechnol. 2011. p. 980286.
4.
Sasaki M, Honmou O. Mesenchymal Stem Cell. Cell Therapy Against Cerebral Stroke : Comprehensive Reviews for Translational Researcher and CLinical Trial. 1st ed. Japan. Springer; 2017. p. 147–55.
5.
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. p. 650.
6.
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. p. 2234–45.
7.
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. p. 149–60.
8.
Tackey E, Lipsky P, Illei G. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus. 2004. p. 333–43.
9.
Hofmann K, Clauder A, Manz R. Targeting B cells and plasma cells in autoimmune diseases. Front Immunol. 2018. p. 835.
10.
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. p. 347141.
11.
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. p. 146–53.
12.
Duff M, Ritter T, Ceredig R, Griffi M. Mesenchymal stem cell eff ects on T-cell eff ector pathways. Stem Cell Res Ther. 2011. p. 1–9.
13.
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. p. 743–8.
14.
Dominici M, Blanc K, Le, Mueller I, Slaper-Cortenbach I, Marini F, et al. Keating TRANSPARENCY DECLARATION Conflicts of interest: None to declare.
15.
Prockop A, Horwitz D, E. The International Society for Cellular Therapy position statement. Cytotherapy. 2006. p. 315–7.
16.
Keating A. Mesenchymal stromal cells: New directions. Cell Stem Cell. 2012. p. 709–16.
17.
Rodríguez-Rodríguez N, Rosetti F, Crispín J, Cells. Systemic Lupus Erythematosus: Basic, Applied and Clinical Aspects. Elsevier; 2016. p. 113–9.
18.
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. p. 615–35.
19.
Sanz I, Lee FH, Sanz. Nat Rev Rheumatol -B cells as therapeutic targets in SLE. Nat Rev Rheumatol. 2010. p. 326–37.
20.
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. p. 65.
21.
Bernardo M, Fibbe W. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell. 2013. p. 392–402.
22.
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. p. 1045–54.
23.
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. p. 1779–83.
24.
Wan Y, Flavell R. Yin-Yang" functions of transforming growth factor-β and T regulatory cells in immune regulation. Immunol Rev. 2007. p. 199–213.
25.
Chen W, Konkel J. TGF-β and “‘Adaptive’” Foxp 3+ regulatory T cells. J Mol Cell Biol. 2010. p. 30–6.
26.
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. p. 2847–61.
27.
Davis L, Hutcheson J, Mohan C. The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus. J Interf Cytokine Res. 2011. p. 781–9.
28.
Tanaka T, Narazaki M, Kishimoto T. IL-6 in Inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014. p. 16295.
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