PKAI as a potential target for therapeutic intervention.
Drug News Perspect
; 13(1): 12-8, 2000 Feb.
Article
em En
| MEDLINE
| ID: mdl-12937648
ABSTRACT
We have mapped a molecular mechanism for the impaired T-cell function in HIV infection and common variable immunodeficiency (CVI). Protein kinase A type I (PKAI) has a key role as an inhibitor of immune function in T lymphocytes and is activated following antigen receptor triggering. T cells from patients with HIV infection and CVI have increased activation of PKAI. This inhibits immune function and proliferation of T cells. Selective antagonists that block cAMP action through PKAI improve the immune function of T cells from HIV-infected patients up to 300%. Furthermore, combination of cAMP antagonists with interleukin-2 normalized immune responses of T cells from all patients examined and stimulated immune function of T cells from HIV-infected patients up to 600%. In addition, in vitro experiments indicate that approximately 50% of patients with CVI have a T-cell dysfunction that might benefit from a treatment reversing PKAI hyperactivation. This outlines PKAI as a potentially attractive drug target for immunomodulating therapy in HIV infection, as well as for the treatment of other immunodeficiency disorders such as CVI.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Drug News Perspect
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Noruega