BACKGROUND: Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases. Little is known about its role in inflammatory heart disease. METHODS AND RESULTS: We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality. Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-) mice showed persistent disease. The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-gammaR(-/-) hearts. Treatment of wild-type mice with the nitric oxide synthetase inhibitor N:-nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis. CONCLUSIONS: Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.
BACKGROUND:Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases. Little is known about its role in inflammatory heart disease. METHODS AND RESULTS: We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality. Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-)mice showed persistent disease. The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-gammaR(-/-) hearts. Treatment of wild-type mice with the nitric oxide synthetase inhibitor N:-nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis. CONCLUSIONS: Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.
Authors: Marina Afanasyeva; Dimitrios Georgakopoulos; Diego F Belardi; Djahida Bedja; Delisa Fairweather; Yan Wang; Ziya Kaya; Kathleen L Gabrielson; E Rene Rodriguez; Patrizio Caturegli; David A Kass; Noel R Rose Journal: Proc Natl Acad Sci U S A Date: 2004-12-20 Impact factor: 11.205
Authors: Jobert G Barin; Monica V Talor; Nicola L Diny; SuFey Ong; Julie A Schaub; Elizabeth Gebremariam; Djahida Bedja; Guobao Chen; Hee Sun Choi; Xuezhou Hou; Lei Wu; Ashley B Cardamone; Daniel A Peterson; Noel R Rose; Daniela Čiháková Journal: Exp Mol Pathol Date: 2017-08-16 Impact factor: 3.362
Authors: DeLisa Fairweather; Sylvia Frisancho-Kiss; Susy A Yusung; Masheka A Barrett; Sarah E Davis; Shannon J L Gatewood; Dolores B Njoku; Noel R Rose Journal: Am J Pathol Date: 2004-12 Impact factor: 4.307
Authors: Jobert G Barin; G Christian Baldeviano; Monica V Talor; Lei Wu; SuFey Ong; DeLisa Fairweather; Djahida Bedja; Natalie R Stickel; Jillian A Fontes; Ashley B Cardamone; Dongfeng Zheng; Kathleen L Gabrielson; Noel R Rose; Daniela Ciháková Journal: J Immunol Date: 2013-09-18 Impact factor: 5.422
Authors: A Pettersson; X-C Wu; C Ciumas; H Lian; V Chirsky; Y-M Huang; B Bjelke; H Link; B-G Xiao Journal: Clin Exp Immunol Date: 2004-09 Impact factor: 4.330