Lipopolysaccharide suppresses HIV-1 replication in human monocytes by protein kinase C-dependent heme oxygenase-1 induction
Lipopolysaccharide suppresses HIV-1 replication in human monocytes by protein kinase C-dependent heme oxygenase-1 induction
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DOI：
10.1189/jlb.0307172
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发表时间：
2010-05-01
影响因子：
5.5
通讯作者：
Dhawan, Subhash
中科院分区：
文献类型：
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作者：
Devadas, Krishnakumar;Hewlett, Indira K.;Dhawan, Subhash
LPS是革兰氏阴性菌细胞壁的重要组成部分。它激活单核细胞并诱导多种宿主免疫和炎症反应。有趣的是，尽管诱导宿主炎症反应，LPS也保护单核细胞衍生的巨噬细胞免受HIV-1感染。在这份报告中，我们已经表明，LPS治疗的人单核细胞衍生的巨噬细胞显着抑制HIV-1的复制，即使在除了感染细胞感染后24小时。HIV-1复制的抑制与PKC依赖的HO-1诱导相关，HO-1是一种已知分解代谢血红素的细胞保护酶。用PKC抑制剂Go 6976预处理不仅显著抑制LPS介导的HO-1诱导，而且减弱LPS诱导的HIV复制抑制。JNK、NF-κ B和PI 3 K抑制剂显著降低HIV复制与LPS介导的抗HIV作用无关。HO-1的特异性通过用SnPP IX（HO-1酶活性的抑制剂）预处理细胞来实质性逆转LPS诱导的病毒复制来证实。这些结果证明了HO-1在LPS介导的HIV-1复制抑制中作为宿主防御机制的先前未定义的功能。J. Leukoc. 87：915-924; 2010.
LPS is an important component of the Gram-negative bacteria cell wall. It activates monocytes and induces multiple host immune and inflammatory responses. Interestingly, in spite of inducing host-inflammatory responses, LPS also protects monocyte-derived macrophages from infection by HIV-1. In this report, we have shown that LPS treatment of human monocyte-derived macrophages markedly suppressed HIV-1 replication, even on addition to infected cells 24 h after infection. Inhibition of HIV-1 replication was associated with PKC-dependent induction of HO-1, a cytoprotective enzyme known to catabolize heme. Pretreatment with the PKC inhibitor Go 6976 not only substantially inhibited LPS-mediated induction of HO-1 but also attenuated LPS-induced suppression of HIV replication. Significant reduction of HIV replication by inhibitors of JNK, NF-kappa B, and PI3K was independent of a LPS-mediated anti-HIV effect. Specificity of HO-1 was confirmed by substantial reversal of LPS-induced viral replication by pretreatment of cells with SnPP IX, an inhibitor of HO-1 enzyme activity. These results demonstrate a previously undefined function of HO-1 as a host defense mechanism in LPS-mediated inhibition of HIV-1 replication. J. Leukoc. Biol. 87: 915-924; 2010.