ROLIPRAM, A SPECIFIC TYPE-IV PHOSPHODIESTERASE INHIBITOR, IS A POTENT INHIBITOR OF HIV-1 REPLICATION
ROLIPRAM, A SPECIFIC TYPE-IV PHOSPHODIESTERASE INHIBITOR, IS A POTENT INHIBITOR OF HIV-1 REPLICATION
复制标题
DOI：
10.1097/00002030-199510000-00004
复制
发表时间：
1995-10-01
期刊：
影响因子：
3.8
通讯作者：
ENDRES, S
中科院分区：
文献类型：
--
作者：
ANGEL, JB;SAGET, BM;ENDRES, S
目的：为了确定咯利普兰，一种特定的IV型磷酸二酯酶抑制剂，对肿瘤坏死因子（TNF）-α的生产和HIV-1 replication.Design的影响：TNF-α增强HIV-1在体外的复制;阻断TNF-α，从而抑制HIV-1复制可能因此潜在地延迟HIV疾病的进展。喷替福林是一种非特异性磷酸二酯酶抑制剂，可在体外阻断TNF-α合成和HIV-1复制，初步临床研究显示可减少HIV-1感染患者的病毒复制。咯利普兰选择性抑制单核细胞的主要磷酸二酯酶同工酶，抑制脂多糖（LPS）诱导的TNF-α的效力比戊茶碱高500倍。因此，我们假设，咯利普兰将是一个强大的抑制剂的HIV-1 replication.Methods：TNF-α的生产和HIV-1复制咯利普兰和喷替福林的影响进行了测定，在感染和未感染的外周血单核细胞（PBMC），在慢性感染的前单核细胞系（U1）和急性感染的单核细胞系（BT4A3.5）。结果：Rolipram抑制LPS和佛波酯（PMA）刺激的PBMC和PMA刺激的U1细胞中TNF-α的产生。Rolipram还抑制U1细胞系以及急性感染的PBMC和BT4A3.5细胞中的HIV-1复制。根据实验条件，咯利普兰是10-600倍更有效的，在摩尔的基础上，比pendulfylline.Conclusion：咯利普兰是一种有效的抑制剂HIV-1复制，因此值得进一步研究作为一个潜在的治疗剂在治疗HIV-1感染的患者。
Objective: To determine the effects of rolipram, a specific type IV phosphodiesterase inhibitor, on tumor necrosis factor (TNF)-alpha production and HIV-1 replication.Design: TNF-alpha enhances HIV-1 replication in vitro; blocking TNF-alpha and thereby inhibiting HIV-1 replication may therefore potentially delay progression of HIV disease. Pentoxifylline is a non-specific phosphodiesterase inhibitor that blocks TNF-alpha synthesis and HIV-1 replication in vitro and has been shown in preliminary clinical studies to decrease viral replication in HIV-1-infected patients. Rolipram, which selectively inhibits the predominant phosphodiesterase isoenzyme of monocytes, inhibits lipopolysaccharide (LPS)-induced TNF-alpha with 500-fold greater potency than pentoxifylline. We, therefore, hypothesized that rolipram would be a powerful inhibitor of HIV-1 replication.Methods: The effects of rolipram and pentoxifylline on TNF-alpha production and HIV-1 replication were determined in infected and uninfected peripheral blood mononuclear cells (PBMC), in a chronically infected promonocytic cell line (U1) and in an acutely infected monocytic cell line (BT4A3.5). TNF-alpha was determined by specific radioimmunoassay and HIV-1 replication was measured by p24 antigen and HIV-1 mRNA production.Results: Rolipram inhibited TNF-alpha production in LPS- and phorbol myristate acetate (PMA)-stimulated PBMC and in PMA-stimulated U1 cells. Rolipram also inhibited HIV-1 replication in the U1 cell line, as well as in acutely infected PBMC and BT4A3.5 cells. Depending on the experimental conditions, rolipram was 10-600 times more potent, on a molar basis, than pentoxifylline.Conclusion: Rolipram is a potent inhibitor HIV-1 replication and therefore deserves further investigation as a potential therapeutic agent in the treatment of HIV-1-infected patients.