Hydrodynamics-based delivery of an interleukin-1 receptor II fusion gene ameliorates rat autoimmune myocarditis by inhibiting IL-1 and Th17 cell polarization

Chang,He; Wang,Yan; Wu,Weiyin; Li,Gang; Hanawa,Haruo; Zou,Jun

doi:10.3892/ijmm.2013.1276

Hydrodynamics-based delivery of an interleukin-1 receptor II fusion gene ameliorates rat autoimmune myocarditis by inhibiting IL-1 and Th17 cell polarization

Authors:
- He Chang
- Yan Wang
- Weiyin Wu
- Gang Li
- Haruo Hanawa
- Jun Zou
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Affiliations: Division of Cardiology, The Affiliated Zhongshan Hospital of Xiamen University, Xiamen Heart Center, Xiamen, Fujian, P.R. China, Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan, Department of Pharmacology, School of Medical Sciences, Xiamen University, Xiamen, Fujian, P.R. China
Published online on: February 11, 2013 https://doi.org/10.3892/ijmm.2013.1276
Pages: 833-840

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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.

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