title: Hydrodynamic-based delivery of an interleukin-22-Ig fusion gene ameliorates experimental autoimmune myocarditis in rats.
abstract: IL-22 is one of several cytokines with limited homology to IL-10. However, the biological activities of IL-22 are mostly unknown. The purpose of this study was to evaluate the effect of IL-22 on rat experimental autoimmune myocarditis (EAM) and elucidate an aspect of the biological activities of IL-22. Rats were immunized on day 0; IL-22-Ig-treated rats were injected with pCAGGS-IL-22-Ig and control rats with pCAGGS-Ig using hydrodynamics-based gene delivery on day 1 or day 6. IL-22-Ig gene therapy administered on day 1 or day 6 after immunization was effective in controlling EAM as monitored by the heart weight to body weight ratio, and the myocarditis area in rats was sacrificed on day 17. Examination of the expression of IL-22-related genes in purified cells from EAM hearts suggested that IL-22-Ig acting target cells were noncardiomyocytic (NC) noninflammatory cells such as fibroblasts, smooth muscle cells, and endothelial cells. Therefore, we examined the effect of rIL-22 or serum containing IL-22-Ig on the expression of immune-relevant genes in IL-1-stimulated NC cells cultured from EAM hearts. Results showed that the expression of immunologic molecules (PGE synthase, cyclooxygenase-2, MIP-2, MCP-1, IL-6, and cytokine-induced neutrophil chemoattractant-2) in IL-1-stimulated NC cells was significantly decreased by rIL-22 or serum containing IL-22-Ig. EAM was suppressed by hydrodynamics-based delivery of plasmid DNA encoding IL-22-Ig, and the reason for this effectiveness may be that IL-22 suppressed gene expression of PG synthases, IL-6, and chemokines in activated NC noninflammatory cells.
authors.affiliation: Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: He
authors.initials: H
authors.lastname: Chang
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: Raafat
authors.initials: R
authors.lastname: Elnaggar
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 / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D002478:Cells, Cultured; D004247:DNA / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems; D050939:Gene Fusion; D015316:Genetic Therapy; D007136:Immunoglobulins / Q000008:administration & dosage / Q000235:genetics; D007378:Interleukins / Q000008:administration & dosage / Q000235:genetics*; D007958:Leukocyte Count; D008297:Male; D009205:Myocarditis / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D010957:Plasmids / Q000008:administration & dosage; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics*; D000097043:Interleukin-22
chemical_list: D004247:DNA; D007136:Immunoglobulins; D007378:Interleukins; D011993:Recombinant Fusion Proteins; D000097043:Interleukin-22