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2018 | 23 |

Tytuł artykułu

Increased expression and functionality of the gap junction in peripheral blood lymphocytes is associated with hypertension-mediated inflammation in spontaneously hypertensive rats

Autorzy

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Background: Imbalances in circulating T lymphocytes play critical roles in the pathogenesis of hypertension-mediated inflammation. Connexins (Cxs) in immune cells are involved in the maintenance of homeostasis of T lymphocytes. However, the association between Cxs in peripheral blood T lymphocytes and hypertensionmediated inflammation remains unknown. This study was designed to investigate the role of Cxs in T lymphocytes in hypertension-mediated inflammation in spontaneously hypertensive rats (SHRs). Methods: The systolic blood pressure (SBP) in Wistar-Kyoto (WKY) rats and SHRs was monitored using the tail-cuff method. The serum cytokine level was determined using ELISA. The proportions of different T-lymphocyte subtypes in the peripheral blood, the expressions of Cx40/Cx43 in the T-cell subtypes, and the gap junctional intracellular communication (GJIC) of peripheral blood lymphocytes were measured using flow cytometry (FC). The accumulations of Cx40/Cx43 at the plasma membrane and/or in the cytoplasm were determined using immunofluorescence staining. The in vitro mRNA levels of cytokines and GJIC in the peripheral blood lymphocytes were respectively examined using real-time PCR and FC after treatment with Gap27 and/or concanavalin A (Con A). Results: The percentage of CD4+ T cells and the CD4+ /CD8+ ratio were high, and the accumulation or expressions of Cx40/Cx43 in the peripheral blood lymphocytes in SHRs were higher than in those of WKY rats. The percentage of CD8+ and CD4+ CD25+ T cells was lower in SHRs. The serum levels of IL-2, IL-4 and IL-6 from SHRs were higher than those from WKY rats, and the serum levels of IL-2 and IL-6 positively correlated with the expression of Cx40/Cx43 in the peripheral blood T lymphocytes from SHRs. The peripheral blood lymphocytes of SHRs exhibited enhanced GJIC. Cx43-based channel inhibition, which was mediated by Gap27, remarkably reduced GJIC in lymphocytes, and suppressed IL-2 and IL-6 mRNA expressions in Con A stimulated peripheral blood lymphocytes.

Słowa kluczowe

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-

Rocznik

Tom

23

Opis fizyczny

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Twórcy

autor
  • Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002, People’s Republic of China
  • Department of Pathophysiology, Medical College of Shihezi University, Shihezi, Xinjiang, China
autor
  • Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002, People’s Republic of China
autor
  • Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002, People’s Republic of China
autor
  • Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002, People’s Republic of China
autor
  • Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002, People’s Republic of China
autor
  • Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002, People’s Republic of China
  • Department of Pathophysiology, Medical College of Shihezi University, Shihezi, Xinjiang, China

Bibliografia

  • 1. Chen S, Agrawal DK. Dysregulation of T cell subsets in the pathogenesis of hypertension. Curr Hypertens Rep. 2015;17:8.
  • 2. Marvar PJ, Vinh A, Thabet S, et al. T lymphocytes and vascular inflammation contribute to stress-dependent hypertension. Biol Psychiatry. 2012;71:774–82.
  • 3. Harrison DG, Vinh A, Lob H, Madhur MS. Role of the adaptive immune system in hypertension. Curr Opin Pharmacol. 2010;10:203–7.
  • 4. Virdis A, Dell'Agnello U, Taddei S. Impact of inflammation on vascular disease in hypertension. Maturitas. 2014;8:179–83.
  • 5. Tipton AJ, Sullivan JC. Sex differences in T cells in hypertension. Clin Ther. 2014;36:1882–900.
  • 6. Guzik TJ, Hoch NE, Brown KA, et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007;204:2449–60.
  • 7. Solak Y, Afsar B, Vaziri ND, et al. Hypertension as an autoimmune and inflammatory disease. Hypertens Res. 2016;39:567–73.
  • 8. Idris-Khodja N, Mian MO, Paradis P, Schiffrin EL. Dual opposing roles of adaptive immunity in hypertension. Eur Heart J. 2014;35:1238–44.
  • 9. Tinsley JH, Chiasson VL, South S, et al. Immunosuppression improves blood pressure and endothelial function in a rat model of pregnancy-induced hypertension. Am J Hypertens. 2009;22:1107–14.
  • 10. Harrison DG, Marvar PJ, Titze JM. Vascular inflammatory cells in hypertension. Front Physiol. 2012;3:128.
  • 11. Rodriguez-Iturbe B, Pons H, Johnson RJ. Role of the Immune System in Hypertension. Physiol Rev. 2017; 97(3):1127–64.
  • 12. Barhoumi T, Kasal DA, Li MW, et al. T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury. Hypertension. 2011;57:469–76.
  • 13. Matrougui K, Abd Elmageed Z, Kassan M, et al. Natural regulatory T cells control coronary arteriolar endothelial dysfunction in hypertensive mice. Am J Pathol. 2011;178:434–41.
  • 14. Kasal DA, Barhoumi T, Li MW, et al. T regulatory lymphocytes prevent aldosterone-induced vascular injury. Hypertension. 2012;59:324–30.
  • 15. Schiffrin EL. Immune mechanisms in hypertension and vascular injury. Clin Sci (Lond). 2014;126:267–74.
  • 16. Zhang J, Crowley SD. Role of T lymphocytes in hypertension. Curr Opin Pharmacol. 2015;21:14–9.
  • 17. Savoia C, Schiffrin EL. Vascular inflammation in hypertension and diabetes: molecular mechanisms and therapeutic interventions. Clin Sci (Lond). 2007;112:375–84.
  • 18. Willebrords J, Crespo Yanguas S, Maes M, et al. Connexins and their channels in inflammation. Crit Rev Biochem Mol Biol. 2016;51:413–39.
  • 19. Su V, Lau AF. Connexins: mechanisms regulating protein levels and intercellular communication. FEBS Lett. 2014;588: 1212–20.
  • 20. Sáez PJ, Shoji KF, Aguirre A, Sáez JC. Regulation of hemichannels and gap junction channels by cytokines in antigenpresenting cells. Mediat Inflamm. 2014;2014:742734.
  • 21. Neijssen J, Pang B, Neefjes J. Gap junction-mediated intercellular communication in the immune system. Prog Biophys Mol Biol. 2007;94:207–18.
  • 22. Bermudez-Fajardo A, Ylihärsilä M, Evans WH, et al. CD4+ T lymphocyte subsets express connexin 43 and establish gap junction channel communication with macrophages in vitro. J Leukoc Biol. 2007;82:608–12.
  • 23. Glass AM, Snyder EG, Taffet SM. Connexins and pannexins in the immune system and lymphatic organs. Cell Mol Life Sci. 2015;72:2899–910.
  • 24. Elgueta R, Tobar JA, Shoji KF, et al. Gap junctions at the dendritic cell-T cell interface are key elements for antigendependent T cell activation. J Immunol. 2009;183:277–84.
  • 25. Mendoza-Naranjo A, Bouma G, Pereda C, et al. Functional gap junctions accumulate at the immunological synapse and contribute to T cell activation. J Immunol. 2011;187:3121–32.
  • 26. Ni X, Zhang L, Peng M, et al. Hydrogen sulfide attenuates hypertensive inflammation via regulating Connexin expression in spontaneously hypertensive rats. Med Sci Monit. 2018;24:1205–18.
  • 27. Ni X, Wang A, Zhang L, et al. Up-regulation of gap junction in peripheral blood T lymphocytes contributes to the inflammatory response in essential hypertension. PLoS One. 2017;12(9):e0184773.
  • 28. Shao J, Nangaku M, Miyata T, et al. Imbalance of T-cell subsets in angiotensin II-infused hypertensive rats with kidney injury. Hypertension. 2003;42:31–8.
  • 29. Eugenín EA, Brañes MC, Berman JW, Sáez JC. TNF-alpha plus IFN-gamma induce connexin43 expression and formation of gap junctions between human monocytes/macrophages that enhance physiological responses. J Immunol. 2003;170:1320–8.
  • 30. Oviedo-Orta E, Hoy T, Evans WH. Intercellular communication in the immune system: differential expression of connexin40 and 43, and perturbation of gap junction channel functions in peripheral blood and tonsil human lymphocyte subpopulations. Immunology. 2000;99:578–90.
  • 31. Tittarelli A, Mendoza-Naranjo A, Farías M, et al. Gap junction intercellular communications regulate NK cell activation and modulate NK cytotoxic capacity. J Immunol. 2014;192:1313–9.
  • 32. Oviedo-Orta E, Gasque P, Evans WH. Immunoglobulin and cytokine expression in mixed lymphocyte cultures is reduced by disruption of gap junction intercellular communication. FASEB J. 2001;15:768–74.
  • 33. McMaster WG, Kirabo A, Madhur MS, Harrison DG. Inflammation, immunity, and hypertensive end-organ damage. Circ Res. 2015;116:1022–33.
  • 34. Harrison DG, Guzik TJ, Lob HE, et al. Inflammation, immunity, and hypertension. Hypertension. 2011;57:132–40.
  • 35. Ganta CK, Lu N, Helwig BG, et al. Central angiotensin II-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system. Am J Physiol Heart Circ Physiol. 2005;289(4):H1683–91.
  • 36. Alexander M, O'Connell RM. Noncoding RNAs and chronic inflammation: micro-managing the fire within. BioEssays. 2015;37(9):1005–15.
  • 37. Rodriguez-Iturbe B, Quiroz Y, Ferrebuz A, et al. Evolution of renal interstitial inflammation and NF-kappab activation in spontaneously hypertensive rats. Am J Nephrol. 2004;24:587–94.
  • 38. Pollow DP, Uhrlaub J, Romero-Aleshire M, et al. Sex differences in T-lymphocyte tissue infiltration and development of angiotensin II hypertension. Hypertension. 2014;64:384–90. 39. Amador CA, Barrientos V, Peña J, et al. Spironolactone decreases DOCA-salt-induced organ damage by blocking the activation of T helper 17 and the downregulation of regulatory T lymphocytes. Hypertension. 2014;63:797–803.
  • 40. Zhang HC, Zhang ZS, Zhang L, et al. Connexin 43 in splenic lymphocytes is involved in the regulation of CD4+ CD25+ T lymphocyte proliferation and cytokine production in hypertensive inflammation. Int J Mol Med. 2018;41(1):13–24.
  • 41. De Miguel C, Rudemiller NP, Abais JM, Mattson DL. Inflammation and hypertension: new understandings and potential therapeutic targets. Curr Hypertens Rep. 2015;17:507.
  • 42. Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol. 2010;40:1830–5.
  • 43. Oviedo-Orta E, Perreau M, Evans WH, Potolicchio I. Control of the proliferation of activated CD4+ T cells by connexins. J Leukoc Biol. 2010;88:79–86.
  • 44. Abed A, Dussaule JC, Boffa JJ, et al. Connexins in renal endothelial function and dysfunction. Cardiovasc Hematol Disord Drug Targets. 2014;14:15–21.
  • 45. Abed A, Toubas J, Kavvadas P, et al. Targeting connexin 43 protects against the progression of experimental chronic kidney disease in mice. Kidney Int. 2014;86:768–79.
  • 46. Oviedo-Orta E, Errington RJ, Evans WH. Gap junction intercellular communication during lymphocyte transendothelial migration. Cell Biol Int. 2002;26(3):253–63.
  • 47. Corvalán LA, Araya R, Brañes MC, et al. Injury of skeletal muscle and specific cytokines induce the expression of gap junction channels in mouse dendritic cells. J Cell Physiol. 2007;211:649–60.
  • 48. Wang J, Ma M, Locovei S, et al. Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters. Am J Physiol Cell Physiol. 2007;293:C1112–9.
  • 49. Li X, Zhao H, Tan X, et al. Inhibition of connexin43 improves functional recovery after ischemic brain injury in neonatal rats. Glia. 2015;63(9):1553–67.
  • 50. Sáez JC, Leybaert L. Hunting for connexin hemichannels. FEBS Lett. 2014;588:1205–11.
  • 51. Chanson M, Derouette JP, Roth I, et al. Gap junctional communication in tissue inflammation and repair. Biochim Biophys Acta. 2005;1711(2):197–207.
  • 52. Alves LA, de Carvalho AC, Savino W. Gap junctions: a novel route for direct cell-cell communication in the immune system? Immunol Today. 1998;19(6):269–75.

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

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