Advertisement

Heart and Vessels

, Volume 32, Issue 12, pp 1536–1545 | Cite as

Tumor necrosis factor alpha-stimulated gene-6 (TSG-6) inhibits the inflammatory response by inhibiting the activation of P38 and JNK signaling pathway and decreases the restenosis of vein grafts in rats

  • Chengxin Zhang
  • Biao Zhang
  • Huiping Wang
  • Qianshan Tao
  • Shenglin GeEmail author
  • Zhimin ZhaiEmail author
Original Article

Abstract

This study aims to explore the effects of tumor necrosis factor alpha-stimulated gene-6 (TSG-6) on vascular inflammatory response and vascular injury in grafted vein wall of rats and its possible mechanism. Vascular grafting model was established by modified cuff. The effect of TSG-6 on the inflammatory response and vascular injury of vein graft was investigated. The activation of mast cells and macrophages after LPS stimulation was observed by lentivirus-mediated upregulation or downregulation of TSG-6 expression. The results showed that rhTSG-6 treatment could significantly inhibit the proliferation of venous bridge, decrease macrophage infiltration and smooth muscle cell proliferation. The expression levels of TNF-α and IL-1 in treated group were significantly lower than that of untreated group (P < 0.05), while the expression of IL-10 in treated group were significantly higher than that of untreated group (P < 0.05). The expression levels of P38, p-P38, JNK and p-JNK in venous bridge of rats were significantly lower than those of untreated rats (P < 0.05), while there was no significant difference in the expression level of ERK and p-ERK (P > 0.05). TSG-6 could inhibit the proliferation of mast cells and macrophages and the release of inflammatory cytokines by down regulating the expression levels of P38, p-P38, JNK and p-JNK. TSG-6 can inhibit the inflammatory response of transplanted vein grafts in rats and reduce vascular injury by downregulation of P38 and JNK signaling pathway.

Keywords

Tumor necrosis factor alpha-stimulated gene-6 (TSG-6) Grafted vein Venous bridge Proinflammatory response 

Notes

Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interests.

References

  1. 1.
    Hayward PA, Gordon IR, Hare DL, Matalanis G, Horrigan ML, Rosalion A, Buxton BF (2010) Comparable patencies of the radial artery and right internal thoracic artery or saphenous vein beyond 5 years: results from the radial artery patency and clinical outcomes trial. J Thorac Cardiovasc Surg 139:60–65CrossRefPubMedGoogle Scholar
  2. 2.
    Fitzgibbon GM, Kafka HP, Leach AJ, Keon WJ, Hooper GD, Burton JR (1996) Coronary bypass graft fate and patient outcome: angiographic follow-up of 5065 grafts related to survival and reoperation in 1388 patients during 25 years. J Am Coll Cardiol 28:616–626CrossRefPubMedGoogle Scholar
  3. 3.
    Motwani JG, Topol EJ (1998) Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation 97:916–931CrossRefPubMedGoogle Scholar
  4. 4.
    Desai M, Mirzay-Razzaz J, von Delft D, Sarkar S, Hamilton G, Seifalian AM (2010) Inhibition of neointimal formation and hyperplasia in vein grafts by external stent/sheath. Vasc Med 15:287–297CrossRefPubMedGoogle Scholar
  5. 5.
    Kucukseymen S (2017) Inflammation effects on stent restenosis. Angiology. doi: 10.1177/0003319717701659
  6. 6.
    Zhu Z, Xu R, Zheng X, Wang T, Li D, Wang Y, Liu K (2016) Inhibitory effect of TLR4 gene silencing on intimal hyperplasia of vein grafting. Vasc Endovascular Surg 50:464–469CrossRefPubMedGoogle Scholar
  7. 7.
    Beltran SR, Svoboda KK, Kerns DG, Sheth A, Prockop DJ (2015) Anti-inflammatory protein tumor necrosis factor-α-stimulated protein 6 (TSG-6) promotes early gingival wound healing: an in vivo study. J Periodontol 86:62–71CrossRefPubMedGoogle Scholar
  8. 8.
    Watanabe J, Shetty AK, Hattiangady B, Kim DK, Foraker JE, Nishida H, Prockop DJ (2013) Administration of TSG-6 improves memory after traumatic brain injury in mice. Neurobiol Dis 59:86–99CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Wang S, Lee JS, Hyun J, Kim J, Kim SU, Cha HJ, Jung Y (2015) Tumor necrosis factor-inducible gene 6 promotes liver regeneration in mice with acute liver injury. Stem Cell Res Ther 6:20CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Prockop DJ, Oh JY (2012) Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther 20:14–20CrossRefPubMedGoogle Scholar
  11. 11.
    Szántó S, Bárdos T, Gál I, Glant TT, Mikecz K (2004) Enhanced neutrophil extravasation and rapid progression of proteoglycan-induced arthritis in TSG-6-knockout mice. Arthritis Rheum 50:3012–3022CrossRefPubMedGoogle Scholar
  12. 12.
    Qiu JL, Zhu WL, Lu YJ, Bai ZF, Liu ZG, Zhao P, Sun C, Zhang YB, Li H, Liu W (2015) The selective mGluR5 agonist CHPG attenuates SO2-induced oxidative stress and inflammation through TSG-6/NF-κB pathway in BV2 microglial cells. Neurochem Int 85–86:46–52CrossRefPubMedGoogle Scholar
  13. 13.
    Ge JJ, Zhao ZW, Zhou ZC, Wu S, Zhang R, Pan FM, Abendroth DK (2013) p38 MAPK inhibitor, CBS3830 limits vascular remodelling in arterialised vein grafts. Heart Lung Circ 22:751–758CrossRefPubMedGoogle Scholar
  14. 14.
    Liu Y, Zhang R, Yan K, Chen F, Huang W, Lv B, Sun C, Xu L, Li F, Jiang X (2014) Mesenchymal stem cells inhibit lipopolysaccharide-induced inflammatory responses of BV2 microglial cells through TSG-6. J Neuroinflammation 11:135CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    de Vries MR, Wezel A, Schepers A, van Santbrink PJ, Woodruff TM, Niessen HW, Hamming JF, Kuiper J, Bot I, Quax PH (2013) Complement factor C5a as mast cell activator mediates vascular remodelling in vein graft disease. Cardiovasc Res 97:311–320CrossRefPubMedGoogle Scholar
  16. 16.
    Bot I, de Jager SC, Zernecke A, Lindstedt KA, van Berkel TJ, Weber C, Biessen EA (2007) Perivascular mast cells promote atherogenesis and induce plaque destabilization in apolipoprotein E-deficient mice. Circulation 115:2516–2525CrossRefPubMedGoogle Scholar
  17. 17.
    Bot I, Bot M, van Heiningen SH, van Santbrink PJ, Lankhuizen IM, Hartman P, Gruener S, Hilpert H, van Berkel TJ, Fingerle J, Biessen EA (2011) Mast cell chymase inhibition reduces atherosclerotic plaque progression and improves plaque stability in ApoE−/− mice. Cardiovasc Res 89:244–252CrossRefPubMedGoogle Scholar
  18. 18.
    Bot I, de Jager SC, Bot M, van Heiningen SH, de Groot P, Veldhuizen RW, van Berkel TJ, von der Thüsen JH, Biessen EA (2010) The neuropeptide substance P mediates adventitial mast cell activation and induces intraplaque hemorrhage in advanced atherosclerosis. Circ Res 106:89–92CrossRefPubMedGoogle Scholar
  19. 19.
    Rao KN, Brown MA (2008) Mast cells: multifaceted immune cells with diverse roles in health and disease. Ann N Y Acad Sci 1143:83–104CrossRefPubMedGoogle Scholar
  20. 20.
    Leacche M, Carrier M, Bouchard D, Pellerin M, Perrault LP, Pagá P, Hebert Y, Cartier R (2003) Improving neurologic outcome in off-pump surgery: the “no touch” technique. Heart Surg Forum 6:169–175PubMedGoogle Scholar
  21. 21.
    Yu P, Nguyen BT, Tao M, Jiang T, Ozaki CK (2014) Diet-induced obesity drives negative mouse vein graft wall remodeling. J Vasc Surg 59:1670–1676CrossRefPubMedGoogle Scholar
  22. 22.
    Sun JY, Li C, Shen ZX, Zhang WC, Ai TJ, Du LJ, Zhang YY, Yao GF, Liu Y, Sun S, Naray-Fejes-Toth A, Fejes-Toth G, Peng Y, Chen M, Liu X, Tao J, Zhou B, Yu Y, Guo F, Du J, Duan SZ (2016) Mineralocorticoid receptor deficiency in macrophages inhibits neointimal hyperplasia and suppresses macrophage inflammation through SGK1-AP1/NF-κB pathways. Arterioscler Thromb Vasc Biol 36:874–885CrossRefPubMedGoogle Scholar
  23. 23.
    Lee SY, Bae IH, Sung Park D, Jang EJ, Shim JW, Lim KS, Park JK, Sim DS, Jeong MH (2016) Prednisolone- and sirolimus-eluting stent: anti-inflammatory approach for inhibiting in-stent restenosis. J Biomater Appl 31:36–44CrossRefPubMedGoogle Scholar
  24. 24.
    Holy EW, Jakob P, Eickner T, Camici GG, Beer JH, Akhmedov A, Sternberg K, Schmitz KP, Lüscher TF, Tanner FC (2014) PI3K/p110α inhibition selectively interferes with arterial thrombosis and neointima formation, but not re-endothelialization: potential implications for drug-eluting stent design. Eur Heart J 35:808–820CrossRefPubMedGoogle Scholar
  25. 25.
    Lee TH, Wisniewski HG, Vilcek J (1992) A novel secretory tumor necrosis factor-inducible protein (TSG-6) is a member of the family of hyaluronate binding proteins, closely related to the adhesion receptor CD44. J Cell Biol 116:545–557CrossRefPubMedGoogle Scholar
  26. 26.
    Bárdos T, Kamath RV, Mikecz K, Glant TT (2001) Anti-inflammatory and chondroprotective effect of TSG-6 (tumor necrosis factor-alpha-stimulated gene-6) in murine models of experimental arthritis. Am J Pathol 159:1711–1721CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Hu J, Wan S (2012) External support in preventing vein graft failure. Asian Cardiovasc Thorac Ann 20:615–622CrossRefPubMedGoogle Scholar
  28. 28.
    Foskett AM, Bazhanov N, Ti X, Tiblow A, Bartosh TJ, Prockop DJ (2014) Phase-directed therapy: TSG-6 targeted to early inflammation improves bleomycin-injured lungs. Am J Physiol Lung Cell Mol Physiol 306:L120–L131CrossRefPubMedGoogle Scholar
  29. 29.
    Guo P, Zhang SZ, He H, Zhu YT, Tseng SC (2012) TSG-6 controls transcription and activation of matrix metalloproteinase 1 in conjunctivochalasis. Invest Ophthalmol Vis Sci 53:1372–1380CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Wisniewski HG, Vilcek J (1997) TSG-6: an IL-1/TNF-inducible protein with anti-inflammatory activity. Cytokine Growth Factor Rev 8:143–156CrossRefPubMedGoogle Scholar
  31. 31.
    Kim DS, Lee HJ, Jeon YD, Han YH, Kee JY, Kim HJ, Shin HJ, Kang J, Lee BS, Kim SH, Kim SJ, Park SH, Choi BM, Park SJ, Um JY, Hong SH (2015) Alpha-pinene exhibits anti-inflammatory activity through the suppression of MAPKs and the NF-κB pathway in mouse peritoneal macrophages. Am J Chin Med 43:731–742CrossRefPubMedGoogle Scholar
  32. 32.
    Liu L, Song H, Duan H, Chai J, Yang J, Li X, Yu Y, Zhang X, Hu X, Xiao M, Feng R, Yin H, Hu Q, Yang L, Du J, Li T (2016) TSG-6 secreted by human umbilical cord-MSCs attenuates severe burn-induced excessive inflammation via inhibiting activations of P38 and JNK signaling. Sci Rep 6:30121CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Sismanopoulos N, Delivanis DA, Alysandratos KD, Angelidou A, Therianou A, Kalogeromitros D, Theoharides TC (2012) Mast cells in allergic and inflammatory diseases. Curr Pharm Des 18:2261–2277CrossRefPubMedGoogle Scholar
  34. 34.
    Liu Y, Wang Y, Shi H, Jia L, Cheng J, Cui W, Li H, Li P, Du J (2015) CARD9 mediates necrotic smooth muscle cell-induced inflammation in macrophages contributing to neointima formation of vein grafts. Cardiovasc Res 108:148–158CrossRefPubMedGoogle Scholar

Copyright information

© Springer Japan KK 2017

Authors and Affiliations

  1. 1.Cardiac Surgery DepartmentThe 1st Affiliated Hospital of Anhui Medical UniversityHefeiChina
  2. 2.Hematology DepartmentThe 2nd Affiliated Hospital of Anhui Medical UniversityHefeiChina

Personalised recommendations