Alteration of IL-17 related protein expressions in experimental autoimmune myocarditis and inhibition of IL-17 by IL-10-Ig fusion gene transfer.

Abstract

BACKGROUND:

T-helper (Th)1/Th2 cytokine balance plays an important role in the pathogenesis of myocarditis. Recently, some studies indicate that interleukin (IL)-17, known as a T cell (Th17)-derived proinflammatory cytokine, is the major mediator of tissue inflammation in inflammatory and autoimmune diseases. Experimental autoimmune myocarditis (EAM) is a T cell-mediated autoimmune disease; however, the pathogenic role of IL-17 in the development of rat EAM remains largely unknown.

METHODS AND RESULTS:

In the present study, alterations of IL-17-related protein expressions were investigated and then the effect of hydrodynamic-based delivery of plasmid DNA encoding the IL-10-Ig gene on rat EAM and the effect of IL-10-Ig on IL-17 was evaluated. The results showed that IL-17 was expressed more highly than IFN-gamma expressed by Th1 cells in alphabetaT cells and the peaks of IL-17 related protein expression in the heart were the early phase of EAM. Moreover, we observed that IL-10-Ig gene therapy was effective in controlling EAM and that IL-10-Ig significantly suppressed the expression of IL-17 as well as other proinflammatory cytokines, IL-1beta and TNF-alpha, in IL-1-stimulated splenocytes cultured from EAM rats.

CONCLUSIONS:

IL-17 is highly produced by alphabetaT cells in the early phase of EAM hearts and IL-17 inhibition might be a possible mechanism of the amelioration of EAM by IL-10-Ig treatment. These data suggest that IL-17 produced by Th17 plays an important role in the pathogenesis of rat EAM.

• Authors: He Chang, Haruo Hanawa, Tsuyoshi Yoshida, Manabu Hayashi, Hui Liu, Limin Ding, Keita Otaki, Kazuhisa Hao, Kaori Yoshida, Kiminori Kato, Ken Toba, Makoto Kodama, Hiroki Maruyama, Junichi Miyazaki, Yoshifusa Aizawa
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 72 Issue 5 Pg. 813-9 (May 2008) ISSN: 1346-9843 [Print] Japan
• PMID: 18441464 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulins
• Interleukin-17
• Interleukin-23
• RNA, Messenger
• Receptors, Interleukin
• Receptors, Interleukin-17
• Recombinant Fusion Proteins
• Interleukin-10
• Interferon-gamma

Topics

• Animals
• Autoimmune Diseases (immunology, therapy)
• Cardiomyopathies (immunology, therapy)
• Cells, Cultured
• Disease Models, Animal
• Gene Expression (immunology)
• Genetic Therapy (methods)
• Immunoglobulins (genetics)
• Interferon-gamma (genetics)
• Interleukin-10 (genetics)
• Interleukin-17 (genetics)
• Interleukin-23 (genetics)
• Male
• Myocarditis (immunology, therapy)
• RNA, Messenger (metabolism)
• Rats
• Rats, Inbred Lew
• Receptors, Interleukin (genetics)
• Receptors, Interleukin-17 (genetics)
• Recombinant Fusion Proteins (genetics)
• Spleen (cytology)
• Th1 Cells (immunology)
• Th2 Cells (immunology)