Hepatocyte growth factor ameliorates the progression of experimental autoimmune myocarditis: a potential role for induction of T helper 2 cytokines.
Hepatocyte growth factor (HGF) plays a role in cell protection, antiapoptosis, antifibrosis, and angiogenesis. However, the role of HGF in the immune system is not well defined. We examined the influence of HGF on T cells and the effects of HGF therapy in acute myocarditis. Lewis rats were immunized on day 0 with cardiac myosin to establish experimental autoimmune myocarditis (EAM). Human HGF gene with hemagglutinating virus of the Japan-envelope vector was injected directly into the myocardium on day 0 or on day 14 (two groups of treated rats). Rats were killed on day 21. Expression of c-Met/HGF receptor in splenocytes and myocardial infiltrating cells was confirmed by immunohistochemical staining or FACS analysis. Myocarditis-affected areas were smaller in the treated rats than in control rats. Cardiac function in the treated rats was markedly improved. An antigen-specific T cell proliferation assay was done with CD4-positive T cells isolated from control rats stimulated with cardiac myosin. HGF suppressed T cell proliferation and production of IFN-gamma and increased production of IL-4 and IL-10 secreted from CD4-positive T cells in vitro. Additionally, TUNEL assay revealed that HGF reduced apoptosis in cardiomyocytes. HGF reduced the severity of EAM by inducing T helper 2 cytokines and suppressing apoptosis of cardiomyocytes. HGF has potential as a new therapy for myocarditis.
Futamatsu
Hideki
H
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Suzuki
Jun-ichi
J
Mizuno
Shinya
S
Koga
Noritaka
N
Adachi
Susumu
S
Kosuge
Hisanori
H
Maejima
Yasuhiro
Y
Hirao
Kenzo
K
Nakamura
Toshikazu
T
Isobe
Mitsuaki
M
D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000096:biosynthesis*; D015316:Genetic Therapy; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D009205:Myocarditis / Q000276:immunology / Q000628:therapy*; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D018418:Th2 Cells / Q000276:immunology*; D014162:Transfection
D016207:Cytokines; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met