Hydrodynamic-Based Delivery of an Interleukin-22-Ig Fusion Gene Ameliorates Experimental Autoimmune Myocarditis in Rats | Zendy

He Chang | Zendy; Haruo Hanawa | Zendy; Hui Liu | Zendy; Tsuyoshi Yoshida | Zendy; Manabu Hayashi | Zendy; Ritsuo Watanabe | Zendy; Satoru Abe | Zendy; Ken Toba | Zendy; Kaori Yoshida | Zendy; Raafat Elnaggar | Zendy; Shiro Minagawa | Zendy; Yuji Okura | Zendy; Kiminori Kato | Zendy; Makoto Kodama | Zendy; Hiroki Maruyama | Zendy; Junichi Miyazaki | Zendy; Yoshifusa Aizawa | Zendy

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Hydrodynamic-Based Delivery of an Interleukin-22-Ig Fusion Gene Ameliorates Experimental Autoimmune Myocarditis in Rats

Author(s) -

He Chang,

Haruo Hanawa,

Hui Liu,

Tsuyoshi Yoshida,

Manabu Hayashi,

Ritsuo Watanabe,

Satoru Abe,

Ken Toba,

Kaori Yoshida,

Raafat Elnaggar,

Shiro Minagawa,

Yuji Okura,

Kiminori Kato,

Makoto Kodama,

Hiroki Maruyama,

Junichi Miyazaki,

Yoshifusa Aizawa

Publication year - 2006

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.177.6.3635

Subject(s) - myocarditis , immunology , fusion gene , gene delivery , medicine , interleukin , gene , genetic enhancement , biology , cytokine , genetics

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.

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