title: Effect of hydrodynamics-based delivery of IL-18BP fusion gene  on rat experimental autoimmune myocarditis.
abstract: Interleukin-18 (IL-18) is a powerful and important cytokine in myocarditis. IL-18-binding protein (IL-18BP), a naturally occurring antagonist of IL-18, is presumed to play a vital regulatory function in IL-18-mediated immune responses. The purpose of this study was to evaluate the alterations of IL-18 and its related protein expressions and the effect of hydrodynamics-based delivery of the IL-18BP gene for treatment of rat experimental autoimmune myocarditis (EAM).Rats were immunized on Day 0 and killed on 2, 3 and 4 weeks to determine IL-18 and its related protein expression and target cells in EAM hearts. On Day 6, rats were injected with a recombinant plasmid encoding IL-18BP-Ig or SP-Ig. On Day 17, rats were detected with echocardiography and then be killed. IL-18BP gene therapy was effective in controlling EAM, as monitored by a decreased ratio of heart weight to body weight, reduced myocarditis areas, reduced expression of atrial natriuretic peptide, brain natriuretic peptide, IL-17, IFN-γ, IL-6 and IL-10. Furthermore, the effect of serum containing IL-18BP on the expression of immune-relevant genes in IL-1α-stimulated NC cells and splenocytes cultured from EAM rats was examined. The results showed that IL-18BP significantly suppressed the expression of IL-17 as well as other proinflammatory genes such as transforming growth factor-β, prostaglandin E2 synthase, cyclooxygenase-2 in IL-1α-stimulated NC cells, and IL-18BP also significantly suppressed the expression of IL-17, IL-17R, IL-21 and IL-17-related transcriptional factor retinoic acid-related orphan nuclear receptor, signal transducer and activator of transcription-3 and Foxp3 in IL-1α-stimulated splenocytes cultured from EAM rats. IL-18 and its related protein played an important role on the development of EAM. IL-18BP effectively prevented progression of EAM by blocking IL-17 and related inflammatory genes expression. This might be a possible mechanism of the amelioration of EAM by IL-18BP treatment.
authors.forename: He
authors.initials: H
authors.lastname: Chang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.forename: Guang Wei
authors.initials: GW
authors.lastname: Zhang
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Liao
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Jun
authors.initials: J
authors.lastname: Zou
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D057446:Hydrodynamics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D009205:Myocarditis / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D010957:Plasmids / Q000627:therapeutic use*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; C118370:interleukin-18 binding protein