HIF-1α-dependent gene expression program during the nucleic acid-triggered antiviral innate immune responses
2009
Hong, S.W. (Sungkyunkwan University, Suwon, Republic of Korea) | Yoo, J.W. (Sungkyunkwan University, Suwon, Republic of Korea) | Kang, H.S. (Sungkyunkwan University, Suwon, Republic of Korea) | Kim, S.Y. (Dongguk University, Seoul, Republic of Korea), E-mail: [email protected] | Lee, D.K. (Sungkyunkwan University, Suwon, Republic of Korea), E-mail: [email protected]
Recent studies suggest a novel role of HIF-1α under non-hypoxic conditions, including antibacterial and antiviral innate immune responses. However, the identity of the pathogen-associated molecular pattern which triggers HIF-1α activation during the antiviral response remains to be identified. Here, we demonstrate that cellular administration of double-stranded nucleic acids, the molecular mimics of viral genomes, results in the induction of HIF-1α protein level as well as the increase in HIF-1α target gene expression. Whole-genome DNA microarray analysis revealed that double-stranded nucleic acid treatment triggers induction of a number of hypoxia-inducible genes, and induction of these genes are compromised upon siRNA-mediated HIF-1α knock-down. Interestingly, HIF-1α knock-down also resulted in down-regulation of a number of genes involved in antiviral innate immune responses. Our study demonstrates that HIF-1α activation upon nucleic acid-triggered antiviral innate immune responses plays an important role in regulation of genes involved in not only hypoxic response, but also immune response.
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