title: Hydrodynamics-based delivery of an interleukin-1 receptor II fusion gene ameliorates rat autoimmune myocarditis by inhibiting IL-1 and Th17 cell polarization.
abstract: Type II interleukin-1 receptor (IL-1RII) is a non-signaling decoy receptor that blocks the activity of interleukin-1 (IL-1), a pro-inflammatory cytokine involved in experimental autoimmune myocarditis (EAM). The aim of this study was to examine the effects of hydrodynamics-based delivery of a recombinant plasmid encoding IL-1RII-Ig and to elucidate the role of IL-1RII in EAM rats. Rats were immunized on day 0 and injected with a recombinant plasmid encoding IL-1RII-Ig or pCAGGS-SP-Ig (control plasmid) on day 6. IL-1RII-Ig gene therapy effectively controlled EAM as indicated by a decreased heart weight-to-body weight ratio, reduced areas of myocarditis, reduced expression of genes encoding atrial natriuretic peptide and brain natriuretic peptide in the heart, and improved cardiac function. IL-1RII-Ig significantly inhibited the expression of IL-1-related cytokines such as IL-1β, prostaglandin E2 synthase, cyclooxygenase, and monocyte chemotactic protein-1 in EAM hearts. Furthermore, the effect of serum containing IL-1RII-Ig on the expression of immune-related genes in IL-1-stimulated splenocytes cultured from EAM rats was examined. The results showed that the expression of IL-6, transforming growth factor-β, retinoic acid-related orphan nuclear receptor (RORγt) and IL-17, was significantly decreased upon exposure to serum containing IL-1RII-Ig. In conclusion, hydrodynamics-based delivery of a recombinant plasmid encoding IL-1RII-Ig effectively prevented progression of left ventricular remodeling and myocardial damage in EAM rats. Moreover, IL-1RII may ameliorate experimental autoimmune myocarditis by blocking IL-1 and inhibiting production of the cytokines important for the polarization of T cells toward a Th17 phenotype.
authors: Division of Cardiology, The Affiliated Zhongshan Hospital of Xiamen University, Xiamen Heart Center, Xiamen, Fujian, PR China.
authors: He
authors: H
authors: Chang
authors: Yan
authors: Y
authors: Wang
authors: Weiyin
authors: W
authors: Wu
authors: Gang
authors: G
authors: Li
authors: Haruo
authors: H
authors: Hanawa
authors: Jun
authors: J
authors: Zou
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004562:Electrocardiography; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D009205:Myocarditis / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D053574:Receptors, Interleukin-1 Type II / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism; D014162:Transfection / Q000379:methods*
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D053574:Receptors, Interleukin-1 Type II