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


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.
Chang
He
H
Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Hanawa
Haruo
H
Yoshida
Tsuyoshi
T
Hayashi
Manabu
M
Liu
Hui
H
Ding
Limin
L
Otaki
Keita
K
Hao
Kazuhisa
K
Yoshida
Kaori
K
Kato
Kiminori
K
Toba
Ken
K
Kodama
Makoto
M
Maruyama
Hiroki
H
Miyazaki
Junichi
J
Aizawa
Yoshifusa
Y
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D009202:Cardiomyopathies / Q000276:immunology / Q000628:therapy*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015870:Gene Expression / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D007136:Immunoglobulins / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics*; D020381:Interleukin-17 / Q000235:genetics*; D053759:Interleukin-23 / Q000235:genetics; D008297:Male; D009205:Myocarditis / Q000276:immunology / Q000628:therapy*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D018123:Receptors, Interleukin / Q000235:genetics; D053722:Receptors, Interleukin-17 / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D007136:Immunoglobulins; D020381:Interleukin-17; D053759:Interleukin-23; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10; D007371:Interferon-gamma