Autor: Maria Angelica E. Watanabe, Valeria S. F. Sales, Fernando Luiz De Lucca, Liliana R. de Souza
Rok vydání: 2002
Předmět:
Zdroj: Molecular and Cellular Biochemistry. 238:19-26
ISSN: 0300-8177
DOI: 10.1023/a:1019983102017
Popis: Exogenous RNA molecules can be incorporated into eukaryotic cells and can exert a variety of biological effects. We have previously showed that exogenous RNAs obtained from lymphoid organs of animals immunized with synthetic peptides of HIV-1 are able to induce cell-mediated immune responses. In this study, animals were immunized with a synthetic peptide (pol: 476–484) of HIV-1, referred to as p9, which is a cytotoxic T lymphocyte (CTL) epitope. The RNA extracted from the lymphoid organs of animals immunized with p9 was termed p9-RNA. We have demonstrated that p9-RNA is active in inducing human CTL. The p9-RNA was also able to activate the RNA-dependent protein kinase (PKR) of human lymphocytes. The polyA(+) p9-RNA was the fraction responsible for the activation of this protein kinase. We also found that p9-RNA activates the transcription factor nuclear kappa B (NF-κB) by inducing the degradation of its inhibitor I-κB. Thus, these findings suggest that p9-RNA may act as a regulatory RNA and that the induction of CTL activity by p9-RNA could be mediated by PKR through NF-κB activation. It is known that CTL activity plays an important role in host defense against HIV-1 infection. Elucidating the molecular mechanism of p9-RNA could contribute to determining the basis for the use of p9-RNA as an immunomodulator in HIV-infected patients.
Databáze: OpenAIRE