Analysis of regulatory T cells and helper T cells in myocarditis and its application to the therapy for inflammatory cardiovascular diseases.

• Project/Area Number: 22590805
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Niigata University
• Principal Investigator: KODAMA Makoto 新潟大学, 医歯学系, 准教授 (10242447)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 内科 / 免疫学 / 心筋炎 / Th17 / 実験的自己免疫性心筋炎 / Th1 T細胞 / Th17 T細胞 / 間葉幹細胞 / Fucoidan / ヘム / danger signal / 心筋炎後拡張型心筋症 / PDE阻害薬 / 肥満細胞 / curcumin / Th-17 / IL-17 / IL-23 / 間葉系幹細胞 / lipocalin-2

Research Abstract

Alterations of IL-17-related protein expressions were investigated. The results showed thatIL-17 was expressed more highly than IFN-gamma expressed by Th1 cells in alpha/beta T cells and the peaks of IL-17 related protein expression in the heart were the early phase of EAM. Then we focused on helper T cell differentiation in allogenic FM-MSC administered EAM rats. Administration of FM-MSC improved left ventricular ejection fraction. The percentage of Th1 cells and Th17 cells were significantly reduced by FM-MSC administration. Thus, intravenous administration of allogenic FM-MSCs ameliorates EAM via the suppression of Th1/Th17 immunity.

Research Products

• [Journal Article] Estimation of paracrine signaling using quantitative RT-PCR from multiple patchy lesion samples (2013)
  • Author(s): Jiao S, Hanawa H, Suzuki T, Hu YH,Yoshida K, Ogura M, Ohno Y, Ito M, Kashimura T, Obata H, Kodama M
  • Journal Title: MolCell Probes Volume: 27 Pages: 109-113
  • Peer Reviewed
• [Journal Article] Estimation of paracrine signaling using quantitative RT-PCR from multiple patchy lesion samples. (2013)
  • Author(s): Jiao S
  • Journal Title: Mol Cell Probes Volume: 27 Pages: 109-113
  • Peer Reviewed
• [Journal Article] Quercetin offers cardioprotection against progression of experimental autoimmune myocarditis by suppression of oxidative and endoplasmic reticulum stress via endothelin-1/MAPK signaling (2012)
  • Author(s): Arumugam S, Thandavarayan AR, Arozal W, Sari RF, Giridharan VV, Soetikno V, Palaniyandi SS, Harima M, Suzuki K, Nagata M, Takagi R, Kodama M, Watanabe K
  • Journal Title: Free Radical Research Volume: 46 Pages: 154-163
  • Peer Reviewed
• [Journal Article] Systemic transplantation of allogenic fetal membrane-derived mesenchymal stem cells suppresses Th1 and Th17 T cell responses in experimental autoimmune myocarditis (2012)
  • Author(s): Ohshima M, Yamahara K, Ishikane S,Harada K, Tsuda H, Otani K, TaguchiA, Miyazato M, Katsuragi S, Yoshimatsu J, Kodama M, Kangawa K,Ikeda T
  • Journal Title: J Mol Cell Cardiol Volume: 53(3) Pages: 420-8
  • Peer Reviewed
• [Journal Article] Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy (2012)
  • Author(s): Arumugam S, Thandavarayan RA,Veeraveedu PT, Nakamura T, Arozal W, Sari FR, Giridharan VV, Soetikno V, Palaniyandi SS, Harima M, Suzuki K, Nagata M, Kodama M, Watanabe K
  • Journal Title: J Cell Mol Med Volume: 16(9) Pages: 2176-85
  • Peer Reviewed
• [Journal Article] Modulation of endoplasmic reticulum stress and cardiomyocyte apoptosis by mulberry leaf diet in experimental autoimmune myocarditis rats (2012)
  • Author(s): Arumugam S, Thandavarayan RA,Veeraveedu PT, Ma M, Giridharan VV, Arozal W, Sari FR, Sukumaran V,Lakshmanan A, Soetikno V, Suzuki K, Kodama M, Watanabe K
  • Journal Title: J Clin Biochem Nutr Volume: 50(2) Pages: 139-44
  • NAID: 130004466682
  • Peer Reviewed
• [Journal Article] Olmesartan medoxomil treatment potently improves cardiac myosin-induced dilated cardiomyopathy via the modulation of ACE-2 and ANG 1-7 mas receptor (2012)
  • Author(s): Sukumaran V, Veeraveedu PT, Lakshmanan AP, Gurusamy N, Yamaguchi K, Ma M, Suzuki K, Kodama M, Watanabe K
  • Journal Title: Free Radic Res Volume: 46(7) Pages: 850-60
  • Peer Reviewed
• [Journal Article] Involvement of AMPK and MAPK signaling during the progression of experimental autoimmune myocarditis in rats and its blockade using a novel antioxidant (2012)
  • Author(s): Arumugam S, Thandavarayan RA, Veeraveedu PT, Giridharan VV,Soetikno V, Harima M, Suzuki K, Nagata M, Tagaki R, Kodama M, Watanabe K
  • Journal Title: Exp Mol Pathol Volume: 93(2) Pages: 183-9
  • Peer Reviewed
• [Journal Article] Telmisartan acts through the modulation of ACE-2/ANG 1-7/mas receptor in rats with dilated cardiomyopathy induced by experimental autoimmune myocarditis (2012)
  • Author(s): Sukumaran V, Veeraveedu TP, Gurusamy N, Lakshmanan PA, Yamaguchi K, Ma M, Suzuki K, Kodama M, Watanabe K
  • Journal Title: Life Sciences Volume: 90 Pages: 289-300
  • Peer Reviewed
• [Journal Article] Candesartan cilexetil protects from cardiac myosin induced cardiotoxicity via reduction of endoplasmic reticulum stress and apoptosis in rats: Involvement of ACE2-Ang (1-7)-mas axis (2012)
  • Author(s): Arumugam S, Thandavarayan AR, Palaniyandi SS, Giridharan VV, Arozal W, Sari RF, Soetikno V, Harima M, Suzuki K, Kodama M, Watanabe K
  • Journal Title: Toxicology Volume: 291 Pages: 139-145
  • Peer Reviewed
• [Journal Article] Involvement of AMPK and MAPK signaling during the progression of experimental autoimmune myocarditis in rats and its blockade using a novel antioxidant. (2012)
  • Author(s): Arumugam S
  • Journal Title: Exp Mol Pathol Volume: 93 Pages: 183-189
  • Peer Reviewed
• [Journal Article] Olmesartan medoxomil treatment potently improves cardiac myosin-induced dilated cardiomyopathy via the modulation of ACE-2 and ANG 1-7 mas receptor. (2012)
  • Author(s): Sukumaran V
  • Journal Title: Free Radic Res Volume: 46 Pages: 850-860
  • Peer Reviewed
• [Journal Article] Modulation of endoplasmic reticulum stress and cardiomyocyte apoptosis by mulberry leaf diet in experimental autoimmune myocarditis rats. (2012)
  • Author(s): Arumugam S
  • Journal Title: J Clin Biochem Nutr Volume: 50 Pages: 139-144
  • Peer Reviewed
• [Journal Article] Systemic transplantation of allogenic fetal membrane-derived mesenchymal stem cells suppresses Th1 and Th17 T cel responses in experimental autoimmune myocarditis. (2012)
  • Author(s): Ohshima M
  • Journal Title: J Mol Cell Cardiol Volume: 53 Pages: 420-428
  • Peer Reviewed
• [Journal Article] Experimental autoimmune myocarditis: role of renin angiotensin system (2011)
  • Author(s): Watanabe K, Arumugam S, Thandavarayan AR, Kodama M
  • Journal Title: Myocarditis. Edited by Daniela Cihakova, InTech - Open Access Publisher Pages: 309-320
  • Peer Reviewed
• [Journal Article] Inhibition of cardiac oxidative and endoplasmic reticulum stress-mediated apoptosis by curcumin treatment contributes to protection against acute myocarditis (2011)
  • Author(s): Mito S, Thandavarayan RA, Ma M, Lakshmanan A, Suzuki K, Kodama M, Watanabe K
  • Journal Title: Free Radical Res Volume: 45 Pages: 1223-1231
  • Peer Reviewed
• [Journal Article] Curcumin ameliorates cardiac inflammation in rats with autoimmune myocarditis (2011)
  • Author(s): Mito S, Watanabe K, Harima M, Thandavarayan RA, Veeraveedu PT, Sukumaran V, Suzuki K, Kodama M, izawa Y
  • Journal Title: Biol Pharm Bull Volume: 34 Pages: 974-979
  • NAID: 130000738083
  • Peer Reviewed
• [Journal Article] A novel phenylpyridazinone, T-3999, reduces the progression of autoimmune myocarditis to dilated cardiomyopathy (2011)
  • Author(s): Kamal FA, Watanabe K, Ma M, Abe Y, Elbarbary R, Kodama M, Aizawa Y
  • Journal Title: Heart Vessels Volume: 26 Pages: 81-90
  • Peer Reviewed
• [Journal Article] Cardioprotective effects of telmisartan against heart failure in rats induced by experimental autoimmune myocarditis through the modulation of angiotensin-converting enzyme-2/angiotensin 1-7/Mas receptor axis (2011)
  • Author(s): Sukumaran V, Veeraveedu TP, Gurusamy N, Yamaguchi K, Lakshmanan PA, Ma M, Suzuki K, Kodama M, Watanabe K
  • Journal Title: Int J Biol Sci Volume: 7 Pages: 1077-1092
  • Peer Reviewed
• [Journal Article] Free heme is a danger signal inducing expression of proinflammatory proteins in cultured cells derived from normal rat hearts (2011)
  • Author(s): Hao K, Hanawa H, Ding L, Ota Y, Yoshida K, Toba K, Ogura M, Ito H, Kodama M, Aizawa Y
  • Journal Title: Mol Immunol Volume: 48 Pages: 1191-1202
  • Peer Reviewed
• [Journal Article] Olmesartan, an AT1 antagonist, attenuates oxidative stress, endoplasmic reticulum stress and cardiac inflammatory mediators in rats with heart failure induced by xperimental autoimmune myocarditis (2011)
  • Author(s): Sukumaran V, Watanabe K, Veeraveedu TP, Gurusamy N, Ma M, Yamaguchi K, Suzuki K, Kodama M, Aizawa Y
  • Journal Title: Int J Biol Sci Volume: 7 Pages: 154-167
  • Peer Reviewed
• [Journal Article] Sulfated polysaccharide fucoidan ameliorates experimental autoimmune myocarditis in rats (2011)
  • Author(s): Tanaka K, Ito M, Kodama M, TomitaM, Kimura S, Hoyano M, Mitsuma W, Hirono S, Hanawa H, Aizawa Y
  • Journal Title: J Cardiovasc Pharmacol Ther Volume: 16 Pages: 79-86
  • Peer Reviewed
• [Journal Article] IL-1 receptor accessory protein-Ig/IL-1 receptor type II-Ig heterodimer inhibits IL-1 response more strongly than other IL-1 blocking biopharmaceutical agents (2011)
  • Author(s): Hanawa H, Ota Y, Ding L, Chang H, Yoshida K, Otaki K, Hao K, Kasahara S, Kodama M, Nakazawa M, Aizawa Y
  • Journal Title: J Clin Immunol Volume: 31 Pages: 455-464
  • Peer Reviewed
• [Journal Article] Telmisartan ameliorates experimental autoimmune myocarditis associated with inhibition of inflammation and oxidative stress (2011)
  • Author(s): Sukumaran V, Watanabe K, Veeraveedu PT, Ma M, Gurusamy N, Rajavel V, Suzuki K, Yamaguchi K, Kodama M, Aizawa Y
  • Journal Title: Eur J Pharmacol Volume: 652 Pages: 126-135
  • Peer Reviewed
• [Journal Article] Free heme is a danger signed inducing expression of proinflammatory proteins in cultured cells derived from normal rat hearts (2011)
  • Author(s): Kazuhisa Hao, et al.
  • Journal Title: Mol Immunol Volume: 48 Issue: 9-10 Pages: 1191-1202
  • DOI: 10.1016/j.molimm.2011.02.013
  • Peer Reviewed
• [Journal Article] A novel phenlpyridazinone, T-3999, reduces the progression of autoimmune myocarditis to dilated cardiomyopathy (2011)
  • Author(s): Fadia Ali Kamal, et al.
  • Journal Title: Heart Vessels Volume: 26 Issue: 1 Pages: 81-90
  • DOI: 10.1007/s00380-010-0018-z
  • Peer Reviewed
• [Journal Article] Inhibition of cardiac oxidative and endoplasmic reticulum stress-mediated apoptosis by curcumin treatment contributes to protection against acute myocarditis (2011)
  • Author(s): Sayaka Mito, et al.
  • Journal Title: Free Radical Research Volume: 45 Issue: 10 Pages: 1223-1231
  • DOI: 10.3109/10715762.2011.607252
  • Peer Reviewed
• [Journal Article] Allogeneic administration of fetal membrane-derived mesenchymal stemcells attenuates acute myocarditis in rats. (2010)
  • Author(s): Ishikane S, Yamahara K, Kodama M (5番目), et al.
  • Journal Title: J Moll Cell Cardiol Volume: 49 Pages: 753-761
  • Peer Reviewed
• [Journal Article] Lipocalin-2/neutrophil gelatinase-B associated lipocalin is strongly induced in heaits of rats with autoimmune myocarditis and in human myocarditis. (2010)
  • Author(s): Ding L, Hanawa H, Kodama M(12番目), et al.
  • Journal Title: Circ J Volume: 74 Pages: 523-530
  • Peer Reviewed
• [Journal Article] The antioxidant edaravone attenuates ER-stress-mediated cardiac apoptosis and dusfunction in rats with autoimmune myocarditis. (2010)
  • Author(s): Shimazaki H, Watanabe K, Kodama M (9番目), et al.
  • Journal Title: Free Radical Research Volume: 44 Pages: 1082-1090
  • Peer Reviewed
• [Presentation] フリーのヘムはTol様受容体を介して心臓在住マクロファージを強力に活性化する (2011)
  • Author(s): 塙晴雄, 他
  • Organizer: 第15回日本心不全学会
  • Place of Presentation: 鹿児島市、かごしま県民交流センター
• [Presentation] Free heme strongly induces pro inflammatory proteins in cultured cells derived from normal rat hearts. (2010)
  • Author(s): 羽尾和久、塙晴雄、小玉誠(7番目), 他
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都
• [Book] 今日の治療指針2011心筋炎 (2011)
  • Author(s): 小玉誠
  • Total Pages: 2
  • Publisher: 医学書院