A novel method of immunomodulation of endothelial cells using Streptococcus pyogenes and its lysate
DOI:
https://doi.org/10.15584/ejcem.2021.2.2Keywords:
biomarkers, endothelial cells, immune-regulation, Streptococcus pyogenesAbstract
Introduction. Coronary artery diseases and autoimmune disorders are common in clinical practice.
Aim. In this study, Streptococcus pyogenes and its lysate were studied to modify the endothelial function.
Material and methods. HUVEC cells were seeded in the cell culture, and Streptococcus pyogenes were added to the cell culture, and the supernatant was studied for the secreted proteins. In the second phase, the bacterial lysate was synthesized, and the lysate was added to cell culture and studied.
Results. When S. pyogenes alone was added to culture, E Cadherin, Angiostatin, EpCAM and PDGF-AB were some of the biomarkers elevated significantly. HCC1, IGFBP2 and TIMP were some of the biomarkers which showed a reduction. When the lysate was added, the cell-culture was maintained for a longer time, and it showed the synthesis of immune regulatory cytokines. Heatmap analysis showed a significant number of proteins/cytokines concerning the immune/pathways, and toll-like receptors superfamily were modified. BLC, IL 17, BMP 7, PARC, Contactin2, IL 10 Rb, NAP 2 (CXCL 7), Eotaxin 2 were maximally increased. By principal component analysis, the results observed were significant.
Conclusion. There is potential for a novel method of immunomodulation of the endothelial cells, which have pleiotropic functions, using S. pyogenes and its lysates.
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References
Negi P, Sondhi S, Asotra S, Mahajan K, Mehta A. Current status of rheumatic heart disease in India. Indian Heart Journal. 2019;71(1):85-90.
Kar P, Geeta K, Gopinath R, Durga P. Mortality prediction in Indian cardiac surgery patients: Validation of European System for Cardiac Operative Risk Evaluation II. Indian Journal of Anaesthesia. 2017;61(2):157.
Srilata M, Padhy N, Padmaja D, Gopinath R. Does Parsonnet scoring model predict mortality following adult cardiac surgery in India? Annals of Cardiac Anaesthesia. 2015;18(2):161.
Davarpasand T, Hosseinsabet A, Jalali A. Concomitant coronary artery bypass graft and aortic and mitral valve replacement for rheumatic heart disease: short- and mid-term outcomes. Interactive CardioVascular and Thoracic Surgery. 2015;21(3):322-328.
Vellingiri R, Ranganathan A, Kumaresan K. Prevalence of CAD in rheumatic heart disease: Is time to redefine the age for screening coronary angiography? IOSR journal of dental and medical sciences. 2018;17(6):21-23.
Akesson P, Moritz L, Truedsson M, Christensson B, von Pawel-Rammingen U. IdeS, a highly specific immunoglobulin G (IgG)-cleaving enzyme from Streptococcus pyogenes, is inhibited by specific IgG antibodies generated during infection. Infect Immun. 2006;74(1):497–503.
von Pawel-Rammingen U, Johansson BP, Björck L. IdeS, a novel streptococcal cysteine proteinase with unique specificity for immunoglobulin G. EMBO J. 2002;21(7):1607–1615.
von Pawel-Rammingen U. Streptococcal IdeS and Its Impact on Immune Response and Inflammation. Journal of Innate Immunity. 2012;4(2):132-140.
Johansson B, Shannon O, Björck L. IdeS: A Bacterial Proteolytic Enzyme with Therapeutic Potential. PLoS ONE. 2008;3(2):e1692.
Stubbs M, Thomas M, Vendramin C, Sonesson E, Kjellman C, Järnum S et al. Administration of immunoglobulin G‐degrading enzyme of Streptococcus pyogenes (IdeS) for persistent anti‐ ADAMTS 13 antibodies in patients with thrombotic thrombocytopenic purpura in clinical remission. British Journal of Haematology. 2018;186(1):137-140.
Courtney H, Pownall H. The Structure and Function of Serum Opacity Factor: A Unique Streptococcal Virulence Determinant That Targets High-Density Lipoproteins. Journal of Biomedicine and Biotechnology. 2010;2010:1-16.
Gillard B, Rosales C, Pillai B, Lin H, Courtney H, Pownall H. Streptococcal Serum Opacity Factor Increases the Rate of Hepatocyte Uptake of Human Plasma High-Density Lipoprotein Cholesterol. Biochemistry. 2010;49(45):9866-9873.
Ramos P, Shedlock A, Langefeld C. Genetics of autoimmune diseases: insights from population genetics. J Hum Genet. 2015;60:657–664.
Rees F, Doherty M, Grainge M, et al. The incidence and prevalence of systemic lupus erythematosus in the UK, 1999–2012. Ann Rheum Dis. 2016;75:136–141.
Johnson AE, Gordon C, Palmer RG, Bacon P A. The prevalence and incidence of systemic lupus erythematosus in Birmingham, England. Relationship to ethnicity and country of birth. Arthritis Rheum. 1995;38:551–558.
Zhu M, Xu W, Wei C, et al. CCL14 serves as a novel prognostic factor and tumor suppressor of HCC by modulating cell cycle and promoting apoptosis. Cell Death Dis. 2019;10:796.
Wittenbecher C, Ouni M, Kuxhaus O, et al. Insulin-Like Growth Factor Binding Protein 2 (IGFBP-2) and the Risk of Developing Type 2 Diabetes. Diabetes. 2018;68(1):188-197.
Yau SW, Azar WJ, Sabin MA, Werther GA, Russo VC. IGFBP-2 - taking the lead in growth, metabolism and cancer. J Cell Commun Signal. 2015;9(2):125–142.
Koyama N, Morisaki N, Saito Y, Sohsohida Y. Regulatory Effects of Platelet-derived Growth Factor-AA Homodimer on Migration of Vascular Smooth Muscle Cells. Journal of biological chemistry. 1992;267(32):22806-22812.
Mamer SB, Chen S, Weddell JC, et al. Discovery of High-Affinity PDGF-VEGFR Interactions: Redefining RTK Dynamics. Sci Rep. 2017;7:16439.
Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008;22(10):1276–1312.
Koyner J, Shaw A, Chawla L, et al. Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term Outcomes in Patients with AKI. Journal of the American Society of Nephrology. 2014;26(7):1747-1754.
de Dios Rosado J, Rodriguez-Sosa M. Macrophage Migration Inhibitory Factor (MIF): A Key Player in Protozoan Infections. International Journal of Biological Sciences. 2011;7(9):1239-1256.
Yue X, Wu L, Hu W. The regulation of leukemia inhibitory factor. Cancer Cell Microenviron. 2015;2(3):e877.
Pećina-Slaus N. Tumor suppressor gene E-cadherin and its role in normal and malignant cells. Cancer Cell Int. 2003;3(1):17.
Nolan K, Thompson T. The DAN family: Modulators of TGF-β signaling and beyond. Protein Science. 2014;23(8):999-1012.
Kattamuri C, Luedeke D, Nolan K, et al. Members of the DAN Family Are BMP Antagonists That Form Highly Stable Noncovalent Dimers. Journal of Molecular Biology. 2012;424(5):313-327.
Huang H, Chen P, Yu C, et al. Epithelial Cell Adhesion Molecule (EpCAM) Complex Proteins Promote Transcription Factor-mediated Pluripotency Reprogramming. Journal of Biological Chemistry. 2011;286(38):33520-33532.
Fretto LJ, Snape AJ, Tomlinson JE, et al. Mechanism of Platelet-derived Growth Factor (PDGF)AA, AB, and BB Binding to alpha and Beta PDGF receptor. J Biol Chem. 1993;268(5):3625-3631.
Sheng J, Xu Z. Three decades of research on angiogenin: a review and perspective. Acta Biochimica et Biophysica Sinica. 2015;48(5):399-410.
Campanacci V, Bishop R, Blangy S, Tegoni M, Cambillau C. The membrane bound bacterial lipocalin Blc is a functional dimer with binding preference for lysophospholipids. FEBS Letters. 2006;580(20):4877-4883.
Gautam V, D’Avanzo C, Hebisch M, et al. BACE1 activity regulates cell surface contactin-2 levels. Mol Neurodegener. 2014;9:4.
Masuda T. Contactin-2/TAG-1, active on the front line for three decades. Cell Adhesion & Migration. 2017;11(5-6):524-531.
Pallante B, Giovannone S, Fang-Yu L, et al. Contactin-2 Expression in the Cardiac Purkinje Fiber Network. Circulation: Arrhythmia and Electrophysiology. 2010;3(2):186-194.
Gaffen SL. An overview of IL-17 function and signaling. Cytokine. 2008;43(3):402–407.
Woo M, Xue K, Liu J, McBride H, Tsang B. Calpain-mediated Processing of p53-associated Parkin-like Cytoplasmic Protein (PARC) Affects Chemosensitivity of Human Ovarian Cancer Cells by Promoting p53 Subcellular Trafficking. Journal of Biological Chemistry. 2011;287(6):3963-3975.
Skaar J, Arai T, DeCaprio J. Dimerization of CUL7 and PARC Is Not Required for All CUL7 Functions and Mouse Development. Molecular and Cellular Biology. 2005;25(13):5579-5589.
Nikolaev A, Li M, Puskas N, Qin J, Gu W. Parc - a cytoplasmic anchor for p53. Cell. 2003;112(1):29-40.
Brown AJ, Sepuru KM, Sawant KV, Rajarathnam K. Platelet-Derived Chemokine CXCL7 Dimer Preferentially Exists in the Glycosaminoglycan-Bound Form: Implications for Neutrophil-Platelet Crosstalk. Front Immunol. 2017;8:1248.
Vu JP, Germano P, Lu Y, Pisegna J. Characterization of the orphan human (C-X-C) chemokine receptor type 7 receptor (CXCL7) on T lymphocyte cells. FASEB J. 2010:4.
Grepin R, Guyot M, Giuliano S, et al. The CXCL7/CXCR1/2 Axis Is a Key Driver in the Growth of Clear Cell Renal Cell Carcinoma. Cancer Research. 2013;74(3):873-883.
Schenk BI, Petersen F, Flad HD, Brandt E. Platelet-derived chemokines CXC chemokine ligand (CXCL)7, connective tissue-activating peptide III, and CXCL4 differentially affect and cross-regulate neutrophil adhesion and transendothelial migration. J Immunol. 2002;169:2602–2610.
Shouval DS, Ouahed J, Biswas A, et al. Interleukin 10 receptor signaling: master regulator of intestinal mucosal homeostasis in mice and humans. Adv Immunol. 2014;122:177–210.
Yoo K, Kim S, Chung J, Chang S. Association of IL10, IL10RA, and IL10RB Polymorphisms with Benign Prostate Hyperplasia in Korean Population. Journal of Korean Medical Science. 2011;26(5):659.
Tian Y, Mollo S, Harrington L, Zajac A. IL-10 Regulates Memory T Cell Development and the Balance between Th1 and Follicular Th Cell Responses during an Acute Viral Infection. The Journal of Immunology. 2016;197(4):1308-1321.
Watanabe K, Jose P, Rankin S. Eotaxin-2 Generation Is Differentially Regulated by Lipopolysaccharide and IL-4 in Monocytes and Macrophages. The Journal of Immunology. 2002;168(4):1911-1918.
Jin Y, Cheng X, Lu J, Li X. Exogenous BMP-7 Facilitates the Recovery of Cardiac Function after Acute Myocardial Infarction through Counteracting TGF-β1 Signaling Pathway. The Tohoku Journal of Experimental Medicine. 2018;244(1):1-6.
Ghosh M, Shen Z, Fahey J, Cu-Uvin S, Mayer K, Wira C. Trappin-2/Elafin: a novel innate anti-human immunodeficiency virus-1 molecule of the human female reproductive tract. Immunology. 2010;129(2):207-219.
Misra P, Lebeche D, Ly H, et al. Quantitation of CXCR4 Expression in Myocardial Infarction Using 99mTc-Labeled SDF-1. Journal of Nuclear Medicine. 2008;49(6):963-969.
Erdag G, Medalie D, Rakhorst H, Krueger G, Morgan J. FGF-7 Expression Enhances the Performance of Bioengineered Skin. Molecular Therapy. 2004;10(1):76-85.
Wang W, Soto H, Oldham E, Buchanan M, Homey B, Catron D et al. Identification of a Novel Chemokine (CCL28), which Binds CCR10 (GPR2). Journal of Biological Chemistry. 2000;275(29):22313-22323.
Zapata J, Perez-Chacon G, Carr-Baena P, et al. CD137 (4-1BB) Signalosome: Complexity Is a Matter of TRAFs. Frontiers in Immunology. 2018;9.
Vinay DS, Kwon BS. 4-1BB (CD137), an inducible costimulatory receptor, as a specific target for cancer therapy. BMB Rep. 2014;47(3):122–129.
Kong DH, Kim YK, Kim MR, Jang JH, Lee S. Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer. Int J Mol Sci. 2018;19(4):1057.
Kim T, Park C, Na H, et al. Ig-like domain 6 of VCAM-1 is a potential therapeutic target in TNFα-induced angiogenesis. Exp Mol Med. 2017;49:e294.
Richards DM, Marschall V, Billian-Frey K, et al. HERA-GITRL activates T cells and promotes anti-tumor efficacy independent of FcγR-binding functionality. J. Immunotherapy Cancer. 2018;7:191.
Lübbers J, Rodríguez E, van Kooyk Y. Modulation of Immune Tolerance via Siglec-Sialic Acid Interactions. Frontiers in Immunology. 2018;9.
Witmer A, van Blijswijk B, Dai J, Hofman P, Partanen T, Vrensen G et al. VEGFR-3 in adult angiogenesis. The Journal of Pathology. 2001;195(4):490-497.
Duffen J, Zhang M, Masek-Hammerman K, et al. Modulation of the IL-33/IL-13 Axis in Obesity by IL-13Rα2. The Journal of Immunology. 2018;200(4):1347-1359.
Sharman JP, Goldschmidt G, Burke JM, et al. CD 30 expresssion in non lymphomatous malignancies. Journal of Clinical Oncology 2012;30:15.
Lebrin F, Deckers M, Bertolino P, Tendijke P. TGF-Beta receptor function in the endothelium. Cardiovascular Research. 2005;65(3):599-608.
Hou T, Tieu BC, Ray S, et al. Roles of IL-6-gp130 Signaling in Vascular Inflammation. Curr Cardiol Rev. 2008;4(3):179–192.
Sánchez-Zamora Y, Rodriguez-Sosa M. The Role of MIF in Type 1 and Type 2 Diabetes Mellitus. Journal of Diabetes Research. 2014;2014:1-6.
Yamada A, Arakaki R, Saito M, Kudo Y, Ishimaru N. Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance. Frontiers in Immunology. 2017;8:408.
Sun J. Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases Are Essential for the Inflammatory Response in Cancer Cells. Journal of Signal Transduction. 2010;2010:1-7.
Grimberg A, Coleman CM, Shi Z, Burns TF, MacLachlan TK, Wang W, El-Deiry WS. Insulin-like growth factor factor binding protein-2 is a novel mediator of p53 inhibition of insulin-like growth factor signaling. Cancer Biol Ther. 2006;5(10):1408-1414.
Rose N. Critical Cytokine Pathways to Cardiac Inflammation. Journal of Interferon & Cytokine Research. 2011;31(10):705-710.
Rahaman SO, Sharma P, Harbor PC, Aman MJ, Vogelbaum MA, Haque SJ. IL-13R(alpha)2, a decoy receptor for IL-13 acts as an inhibitor of IL-4-dependent signal transduction in glioblastoma cells. Cancer Res. 2002;62(4):1103-1109.
Niehrs C. Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene. 2006;25(57):7469-7481.
Medler J, Wajant H. Tumor necrosis factor receptor-2 (TNFR2): an overview of an emerging drug target. Expert Opinion on Therapeutic Targets. 2019;23(4):295-307.
Wei Q, Wang Y, Liu H, et al. The expression and role of activin A and follistatin in heart failure rats after myocardial infarction. International Journal of Cardiology. 2013;168(3):2994-2997.
Mehta V, Besner G. Heparin-Binding Epidermal Growth Factor-Like Growth Factor Inhibits Cytokine-Induced NF-κB Activation and Nitric Oxide Production via Activation of the Phosphatidylinositol 3-Kinase Pathway. The Journal of Immunology. 2005;175(3):1911-1918.
Heltberg ML, Krishna S, Jensen MH. On chaotic dynamics in transcription factors and the associated effects in differential gene regulation. Nat Commun. 2019;10(1):71.
Sivaprakasam S, Shahverdiev EM, Spencer PS, Shore KA. Experimental demonstration of anticipating synchronization in chaotic semiconductor lasers with optical feedback. Phys Rev Lett. 2001;87(15):154101.
Sivaprakasam S, Shore KA. Demonstration of optical synchronization of chaotic external-cavity laser diodes. Opt Lett. 1999;24(7):466-468.
Ichinohe T, Pang I, Kumamoto Y, Peaper D, Ho J, Murray T et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proceedings of the National Academy of Sciences. 2011;108(13):5354-5359.
Chalmers C, Khemlani A, Sohn C, Loh J, Tsai C, Proft T. Streptococcus pyogenes nuclease A (SpnA) mediated virulence does not exclusively depend on nuclease activity. Journal of Microbiology, Immunology and Infection. 2020;53(1):42-48.
Shi Z, Gewirtz AT. Together Forever: Bacterial-Viral Interactions in Infection and Immunity. Viruses. 2018;10(3):122.
Darwin C. Journal of researches into the natural history and geology of the countries visited during the voyage of the H.M.S. Beagle round the world, under the command of Captain Fitz. 1845. Roy, R.N. London: John Murray.
Okada H, Kuhn C, Feillet H, Bach JF. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update. Clin Exp Immunol. 2010;160(1):1–9.
Steincrohn P. The blood sugar and cardiac involvement in rheumatic fever. Journal of the American Medical Association. 1938;111(20):1837.
Barach J. The incidence of rheumatic heart disease among diabetic patients. American Heart Journal. 1926;2(2):196-201.
Blank M, Krause I, Magrini L, Spina G, Kalil J, Jacobsen S et al. Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome. Rheumatology. 2006;45(7):833-841.
Oikonomopoulou K, Brinc D, Kyriacou K and Eleftherios P. Diamandis. Infection and Cancer: Revaluation of the Hygiene Hypothesis. Clin Cancer Res. 2013;19(11):2834-2841.
Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res. 1991;3–11.
Alexandroff AB, Nicholson S, Patel PM, Jackson AM. Recent advances in bacillus Calmette-Guerin immunotherapy in bladder cancer. Immunotherapy. 2010;2:551–560.
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