PMID- 24122347 OWN - NLM STAT- MEDLINE DCOM- 20150623 LR - 20211021 IS - 1591-9528 (Electronic) IS - 1591-8890 (Linking) VI - 14 IP - 4 DP - 2014 Nov TI - Effect of hydrodynamics-based delivery of IL-18BP fusion gene on rat experimental autoimmune myocarditis. PG - 397-408 AB - 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-gamma, IL-6 and IL-10. Furthermore, the effect of serum containing IL-18BP on the expression of immune-relevant genes in IL-1alpha-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-beta, prostaglandin E2 synthase, cyclooxygenase-2 in IL-1alpha-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-1alpha-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. FAU - Chang, He AU - Chang H FAU - Wang, Yan AU - Wang Y FAU - Li, Gang AU - Li G FAU - Zhang, Le AU - Zhang L FAU - Zhang, Guang Wei AU - Zhang GW FAU - Liao, Yan Chun AU - Liao YC FAU - Hanawa, Haruo AU - Hanawa H FAU - Zou, Jun AU - Zou J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Italy TA - Clin Exp Med JT - Clinical and experimental medicine JID - 100973405 RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (interleukin-18 binding protein) SB - IM MH - Animals MH - Autoimmune Diseases/*therapy MH - Disease Models, Animal MH - Genetic Therapy/*methods MH - Hydrodynamics MH - Intercellular Signaling Peptides and Proteins/genetics/*therapeutic use MH - Male MH - Myocarditis/*therapy MH - Myocardium/pathology MH - Plasmids/*therapeutic use MH - Rats MH - Recombinant Fusion Proteins/genetics/therapeutic use MH - Treatment Outcome EDAT- 2013/10/15 06:00 MHDA- 2015/06/24 06:00 CRDT- 2013/10/15 06:00 PHST- 2013/04/02 00:00 [received] PHST- 2013/09/10 00:00 [accepted] PHST- 2013/10/15 06:00 [entrez] PHST- 2013/10/15 06:00 [pubmed] PHST- 2015/06/24 06:00 [medline] AID - 10.1007/s10238-013-0260-7 [doi] PST - ppublish SO - Clin Exp Med. 2014 Nov;14(4):397-408. doi: 10.1007/s10238-013-0260-7.