title: The effect of hydrodynamics-based delivery of an IL-13-Ig fusion gene for experimental autoimmune myocarditis in rats and its possible mechanism.
abstract: Interleukin (IL)-13 is a pleiotropic cytokine secreted by activated Th2 T lymphocytes. Th1 cytokines are assumed to exacerbate and Th2 cytokines to ameliorate rat experimental autoimmune myocarditis (EAM). Here, we examined the effect of IL-13 on EAM, using a hydrodynamics-based delivery of an IL-13-Ig fusion gene, as well as the possible mechanism of its effect. Rats were immunized on day 0, and IL-13-Ig-treated rats were injected with pCAGGS-IL-13-Ig, and control rats with pCAGGS-Ig, on day 1 or 7. On day 17, the IL-13-Ig gene therapy was effective in controlling EAM as monitored by a decreased heart weight/body weight ratio, by reduced myocarditis and by reduced atrial natriuretic peptide mRNA in the heart, as a heart failure marker. On the basis of IL-13 receptor mRNA expression in separated cells from EAM hearts, we proposed that IL-13-Ig target cells were CD11b(+) cells and non-cardiomyocytic noninflammatory (NCNI) cells, such as fibroblasts, smooth muscle or endothelial cells. IL-13-Ig inhibited expression of the genes for prostaglandin E synthase, cyclooxygenase-2, inducible nitric oxide synthase, IL-1beta and TNF-alpha in cultivated cells from EAM hearts, while it enhanced expression of the IL-1 receptor antagonist gene. We conclude that IL-13-Ig ameliorates EAM and suppose that its effectiveness may be due to the influence on these immunologic molecules in CD11b(+) and NCNI cells.
authors.affiliation: Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Raafat
authors.initials: R
authors.lastname: Elnaggar
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Manabu
authors.initials: M
authors.lastname: Hayashi
authors.forename: Ritsuo
authors.initials: R
authors.lastname: Watanabe
authors.forename: Satoru
authors.initials: S
authors.lastname: Abe
authors.forename: Ken
authors.initials: K
authors.lastname: Toba
authors.forename: Kaori
authors.initials: K
authors.lastname: Yoshida
authors.forename: He
authors.initials: H
authors.lastname: Chang
authors.forename: Shiro
authors.initials: S
authors.lastname: Minagawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okura
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Hiroki
authors.initials: H
authors.lastname: Maruyama
authors.forename: Junichi
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D039481:CD11b Antigen / Q000032:analysis; D002478:Cells, Cultured; D015316:Genetic Therapy; D018793:Interleukin-13 / Q000097:blood / Q000235:genetics*; D053661:Interleukin-13 Receptor alpha1 Subunit; D009205:Myocarditis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D018123:Receptors, Interleukin / Q000235:genetics; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics*
chemical_list: D039481:CD11b Antigen; C508185:Il13ra1 protein, rat; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins