title: Attenuation of experimental autoimmune myocarditis by si-RNA mediated CD40 silencing.
abstract: CD40 plays an important role in the pathogenesis of myocarditis, and inhibition of CD40 expression could be a promising treatment for myocarditis. In this study, we used an animal model, experimental autoimmune myocarditis (EAM), to investigate whether CD40 siRNA could be exploited for myocarditis therapy.Lewis rats were immunized with purified porcine cardiac myosin to induce EAM or were injected with phosphate buffered saline (PBS) alone (PBS group), scrambled small interfering RNA (siRNA) (negative control group), or CD40siRNA (CD40 siRNA group).CD40 siRNA treatment suppressed the increase in heart weight/body weight ratio, and attenuated the severity of myocardial lesions. Cytokine production, including Th1-type cytokines, was significantly suppressed in rats with myocarditis after CD40 siRNA treatment; however, production of Th2-type cytokines was higher. Specific knockdown of CD40 in EAM rats resulted in increased FOXP3 gene expression and the CD25+ CD4+ subpopulation of T cells but also a decrease in CD80 and CD86 expression. Lymphocyte (T and B cell) proliferation in response to myosin stimulation was significantly inhibited by CD40 silencing.CD40-siRNA is a useful tool for inhibiting in vivo CD40 expression, and it could have therapeutic potential in the prevention and treatment of myocarditis in humans.
authors.affiliation: Division of Cardiology, Department of Pediatrics, Provincial Hospital Affiliated with Shandong University.
authors.forename: Xin
authors.initials: X
authors.lastname: Gong
authors.forename: Bo
authors.initials: B
authors.lastname: Han
authors.forename: Yong
authors.initials: Y
authors.lastname: Zou
authors.forename: Jiezhong
authors.initials: J
authors.lastname: Wang
authors.forename: Wenwei
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000235:genetics*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D007107:Immune System / Q000378:metabolism; D008297:Male; D009205:Myocarditis / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D011917:Rats, Inbred Lew
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D034741:RNA, Small Interfering