Attenuation of experimental autoimmune myocarditis by blocking T cell activation through 4-1BB pathway.
J Mol Cell Cardiol
; 46(5): 719-27, 2009 May.
Article
en En
| MEDLINE
| ID: mdl-19233196
4-1BB, a member of the tumor necrosis factor receptor (TNFR) family, binds the 4-1BB ligand (4-1BBL), works as a costimulatory molecule, and regulates T cell-mediated immune responses. Although inflammation is an essential pathological feature of myocarditis, the role of 4-1BB in experimental autoimmune myocarditis (EAM) remains unclear. Lewis rats were immunized on day 0 with purified porcine cardiac myosin to establish EAM. 4-1BB-immunoglobulin (4-1BBIg) was administered intraperitoneally (n=6) a total of 9 times (3 times per week). Rats were killed on day 21 to study effects of 4-1BB/4-1BBL pathway blockade. For controls, isotype-matched human IgG was administered in other EAM rats (n=6). Histologic and echocardiographic examination showed development of EAM attenuated by 4-1BBIg. Suppression of mRNA expression for IL-1alpha, IL-1beta, IL-4, IL-6, and TNF-alpha was noted in the heart tissue treated with 4-1BBIg. Treatment with 4-1BBIg reduced production of Th1-type cytokines, and inhibited T cell proliferation in vitro. In the 4-1BB signaling pathway in splenocytes, 4-1BBIg suppressed JNK, p38, and IkappaB activity but not that of ERK1/2. Blockade of T cell activation through the 4-1BB/4-1BBL pathway regulates development of EAM; therefore, 4-1BB may be an effective target for treating myocarditis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
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Activación de Linfocitos
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Linfocitos T
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Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral
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Miocarditis
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Mol Cell Cardiol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido