The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지

Conditioned Medium from Dying Smooth Muscle Cell Induced Apoptotic Death

  • Bu, Moon-Hyun (Department of Pharmacology, College of Medicine, Pusan National University) ;
  • Lee, Kyeong-Ah (Department of Pharmacology, College of Medicine, Pusan National University) ;
  • Kim, Koan-Hoi (Department of Pharmacology, College of Medicine, Pusan National University) ;
  • Rhim, Byung-Yong (Department of Pharmacology, College of Medicine, Pusan National University)
  • Published : 2005.12.21
Download PDF
⟨ Previous Next ⟩

Abstract

In this study, the authors investigated whether death of vascular smooth muscle cell (VSMC) had a pathological pertinence. Conditioned media obtained from rat aorta smooth muscle cell (SMC) that were induced death by expressing FADD in the absence of tetracycline (FADD-SMC) triggered death of normal SMC. DNA fragmentation and caspase-3 activation were observed in dying SMC by conditioned media. FADD-SMC showed transcriptional activation of tumor necrosis factor $(TNF)-{\alpha}$. Conditioned medium contained $TNF-{\alpha}$, indicating secretion of the cytokine from dying FADD-SMC. It was investigated if secreted $TNF-{\alpha}$ was functional. Conditioned medium activated ERK and p38 MAPK pathways and induced MMP-9 expression, whereas depletion of the cytokine with its soluble receptor (sTNFR) remarkably inhibited induction of MMP-9 by conditioned medium. These findings suggest that $TNF-{\alpha}$ in conditioned medium seems to be active. Then, contribution of $TNF-{\alpha}$ on death-inducing activity of conditioned medium was examined. Depletion of $TNF-{\alpha}$ with soluble $TNF-{\alpha}$ receptor decreased the death activity of conditioned medium by 35%, suggesting that $TNF-{\alpha}$ play a partial role in the death activity. Boiling of medium almost completely abolished the death-inducing activity, suggesting that other heat labile death inducing proteins existed in conditioned medium. Taken together, these results indicate that SMC undergoing death could contribute to inflammation by expressing inflammatory cytokines and pathological complications by inducing death of neighboring cells.

Keywords

References

  1. Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3: 745-756, 2003 https://doi.org/10.1038/nri1184
  2. Baker SJ, Reddy EP. Modulation of life and death by the TNF receptor superfamily. Oncogene 17: 3261-3270, 1998
  3. Bauriedel G, Hutter R, Welsch U, Bach R, Sievert H, Luderitz B. Role of smooth muscle cell death in advanced coronary primary lesions: implications for plaque instability. Cardiovasc Res 41: 480-488, 1999 https://doi.org/10.1016/S0008-6363(98)00318-6
  4. Bendeck MP, Zempo N, Clowes AW, Galardy RE, Reidy MA. Smooth muscle cell migration and matrix metalloproteinase expression after arterial injury in the rat. Circ Res 75: 539-545, 1994 https://doi.org/10.1161/01.RES.75.3.539
  5. Bennett MR. Apoptosis of vascular smooth muscle cells in vascular remodelling and atherosclerotic plaque rupture. Cardiovasc Res 41: 361-368, 1999 https://doi.org/10.1016/S0008-6363(98)00212-0
  6. Biancone L, Martino AD, Orlandi V, Conaldi PG, Toniolo A, Camussi G. Development of inflammatory angiogenesis by local stimulation of Fas in vivo. J Exp Med 186: 147-152, 1997 https://doi.org/10.1084/jem.186.1.147
  7. Cai W, Devaux B, Schaper W, Schaper J. The role of Fas/APO 1 and apoptosis in the development of human atherosclerotic lesions. Atherosclerosis 131: 177-186, 1997 https://doi.org/10.1016/S0021-9150(97)06099-1
  8. Chinnaiyan AM, Dixit VM. The cell-death machine. Curr Biol 6: 555-562, 1996 https://doi.org/10.1016/S0960-9822(02)00541-9
  9. Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81: 505-512, 1995 https://doi.org/10.1016/0092-8674(95)90071-3
  10. Chinnaiyan AM, Tepper CG, Seldin MF, O'Rourke K, Kischkel FC, Hellbardt S, Krammer PH, Peter ME, Dixit VM. FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. J Biol Chem 271: 4961-4965, 1996 https://doi.org/10.1074/jbc.271.9.4961
  11. Cho A, Courtman DW, Langille BL. Apoptosis (programmed cell death) in arteries of the neonatal lamb. Circ Res 76: 168-175, 1995 https://doi.org/10.1161/01.RES.76.2.168
  12. Cho A, Graves J, Reidy MA. Mitogen-activated protein kinases mediate matrix metalloproteinase-9 expression in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 20: 2527- 2532, 2000 https://doi.org/10.1161/01.ATV.20.12.2527
  13. Cho A, Reidy MA. Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury. Circ Res 91: 845-851, 2002 https://doi.org/10.1161/01.RES.0000040420.17366.2E
  14. Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. Lab Invest 49: 327-333, 1983
  15. Crisby M, Kallin B, Thyberg J, Zhivotovsky B, Orrenius S, Kostulas V, Nilsson J. Cell death in human atherosclerotic plaques involves both oncosis and apoptosis. Atherosclerosis 130: 17-27, 1997 https://doi.org/10.1016/S0021-9150(96)06037-6
  16. Flynn PD, Byrne CD, Baglin TP, Weissberg PL, Bennett MR. Thrombin generation by apoptotic vascular smooth muscle cells. Blood 89: 4378-4384, 1997
  17. Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 94: 2493-2503, 1994 https://doi.org/10.1172/JCI117619
  18. Geng YJ, Wu Q, Muszynski M, Hansson GK, Libby P. Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin- 1-beta. Arterioscler Thromb Vasc Biol 16: 19-27, 1996 https://doi.org/10.1161/01.ATV.16.1.19
  19. Gum R, Wang H, Lengyel E, Juarez J, Boyd D. Regulation of 92 kDa type IV collagenase expression by the jun aminoterminal kinase- and the extracellular signal-regulated kinase-dependent signaling cascades. Oncogene 14: 1481-1493, 1997 https://doi.org/10.1038/sj.onc.1200973
  20. Henson PM, Bratton DL, Fadok VA. Apoptotic cell removal. Curr Biol 11: R795-R805, 2001 https://doi.org/10.1016/S0960-9822(01)00474-2
  21. Herron GS, Banda MJ, Clark EJ, Gavrilovic J, Werb Z. Secretion of metalloproteinases by stimulated capillary endothelial cells. II. Expression of collagenase and stromelysin activities is regulated by endogenous inhibitors. J Biol Chem 261: 2814-2818, 1986
  22. Idriss HT, Naismith JH. TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech 50: 184-195, 2000 https://doi.org/10.1002/1097-0029(20000801)50:3<184::AID-JEMT2>3.0.CO;2-H
  23. Kockx MM, Herman AG. Apoptosis in atherogenesis: implications for plaque destabilization. Eur Heart J 19(Suppl G): G23-G28, 1998
  24. Kockx MM. Apoptosis in the atherosclerotic plaque: quantitative and qualitative aspects. Arterioscler Thromb Vasc Biol 18: 1519-1522, 1998 https://doi.org/10.1161/01.ATV.18.10.1519
  25. Kockx MM, Herman AG. Apoptosis in atherosclerosis: beneficial or detrimental? Cardiovasc Res 45: 736-746, 2000 https://doi.org/10.1016/S0008-6363(99)00235-7
  26. Libby P, Geng YJ, Sukhova GK, Simon DI, Lee RT. Molecular determinants of atherosclerotic plaque vulnerability. Ann NY Acad Sci 811: 134-142; discussion 142-135, 1997 https://doi.org/10.1111/j.1749-6632.1997.tb51996.x
  27. Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 104: 365-372, 2001 https://doi.org/10.1161/01.CIR.104.3.365
  28. MacEwan DJ. TNF ligands and receptors-$\alpha$ matter of life and death. Br J Pharmacol 135: 855-875, 2002 https://doi.org/10.1038/sj.bjp.0704549
  29. Nagata S. Fas ligand-induced apoptosis. Annu Rev Genet 33: 29- 55, 1999 https://doi.org/10.1146/annurev.genet.33.1.29
  30. Proudfoot D, Skepper JN, Hegyi L, Bennett MR, Shanahan CM, Weissberg PL. Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies. Circ Res 87: 1055-1062, 2000 https://doi.org/10.1161/01.RES.87.11.1055
  31. Schaub FJ, Han DK, Liles WC, Adams LD, Coats SA, Ramachandran RK, Seifert RA, Schwartz SM, Bowen-Pope DF. Fas/ FADD-mediated activation of a specific program of inflammatory gene expression in vascular smooth muscle cells. Nat Med 6: 790- 796, 2000 https://doi.org/10.1038/77521
  32. Simon C, Goepfert H, Boyd D. Inhibition of the p38 mitogenactivated protein kinase by SB203580 blocks PMA-induced Mr 92,000 type IV collagenase secretion and in vitro invasion. Cancer Res 58: 1135-1139, 1998
  33. Van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM. Suppression of TNF-$\alpha$-induced apoptosis by NF-kappaB. Science 274: 787-789, 1996 https://doi.org/10.1126/science.274.5288.787
  34. Vaux DL, Korsmeyer SJ. Cell death in development. Cell 96: 245- 254, 1999 https://doi.org/10.1016/S0092-8674(00)80564-4
  35. Walsh CM, Wen BG, Chinnaiyan AM, O'Rourke K, Dixit VM, Hedrick SM. A role for FADD in T cell activation and development. Immunity 8: 439-449, 1998 https://doi.org/10.1016/S1074-7613(00)80549-X
  36. Wesley RB, 2nd, Meng X, Godin D, Galis ZS. Extracellular matrix modulates macrophage functions characteristic to atheroma: collagen type I enhances acquisition of resident macrophage traits by human peripheral blood monocytes in vitro. Arterioscler Thromb Vasc Biol 18: 432-440, 1998 https://doi.org/10.1161/01.ATV.18.3.432
  37. Yeh WC, Pompa JL, McCurrach ME, Shu HB, Elia AJ, Shahinian A, Ng M, Wakeham A, Khoo W, Mitchell K, El-Deiry WS, Lowe SW, Goeddel DV, Mak TW. FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science 279: 1954-1958, 1998 https://doi.org/10.1126/science.279.5358.1954
  38. Zempo N, Kenagy RD, Au YP, Bendeck M, Clowes MM, Reidy MA, Clowes AW. Matrix metalloproteinases of vascular wall cells are increased in balloon-injured rat carotid artery. J Vasc Surg 20: 209-217, 1994 https://doi.org/10.1016/0741-5214(94)90008-6