NFAT公司
分子生物学
转录因子
转染
抄写(语言学)
生物
转录因子Sp1
细胞外
细胞生物学
发起人
细胞培养
基因表达
基因
生物化学
哲学
遗传学
语言学
作者
Almudena Blanco,Susana Álvarez,Manuel Fresno,María Ángeles Muñoz‐Fernández
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2008-01-01
卷期号:180 (1): 530-540
被引量:24
标识
DOI:10.4049/jimmunol.180.1.530
摘要
Abstract Both the HIV-1 protein Tat and cyclooxygenase-2 (COX-2) have been involved in the neuropathogenesis associated with HIV-1 infection. However, the relationship among them has not been addressed. Here, we found that extracellular Tat was able to induce COX-2 mRNA and protein expression and PGE2 synthesis in astrocytoma cell lines and primary human astrocytes. Moreover, Tat induced COX-2 promoter transcription. Deletion of NF-κB sites of the promoter did not diminish Tat-dependent transcription. Interestingly, Tat did not induce NF-κB activity, suggesting that NF-κB was not necessary to control COX-2 transcription induced by Tat. In contrast, deletion or mutation of the NFAT and/or AP-1 site abrogated COX-2 induction by Tat. Moreover, Tat induced transcription of NFAT- and AP-1-dependent reporter genes. Transfection of a dominant negative c-Jun mutant protein, TAM-67, or of a dominant negative version of NFAT, efficiently blocked the induction of COX-2 promoter by Tat, confirming the requirement of both transcription factors. Moreover, Tat induced NFAT translocation to the nucleus and binding to the distal site of the COX-2 promoter. The importance of NFAT and AP-1 in COX-2 induction and PGE2 synthesis by Tat was corroborated by using pharmacological inhibitors of the NFΑΤ, ERK, and JNK pathways. In summary, our results indicate that HIV-1 Tat was able to induce COX-2 and PGE2 synthesis in astrocytic cells through an NFAT/AP-1-dependent mechanism.
科研通智能强力驱动
Strongly Powered by AbleSci AI