title: 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.
  
  
  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.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: Tsuyoshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Manabu
authors.initials: M
authors.lastname: Hayashi
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Limin
authors.initials: L
authors.lastname: Ding
authors.forename: Keita
authors.initials: K
authors.lastname: Otaki
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Hao
authors.forename: Kaori
authors.initials: K
authors.lastname: Yoshida
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.forename: Ken
authors.initials: K
authors.lastname: Toba
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 / 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
chemical_list: 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