Host chemokine (C-C motif) ligand-2 (CCL2) is differentially regulated in HIV type 1 (HIV-1)-infected individuals
Host chemokine (C-C motif) ligand-2 (CCL2) is differentially regulated in HIV type 1 (HIV-1)-infected individuals
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DOI：
10.1093/intimm/dxl078
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发表时间：
2006-10-01
影响因子：
4.4
通讯作者：
Heiken, Hans
中科院分区：
文献类型：
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作者：
Ansari, Abdul Wahid;Bhatnagar, Nupur;Heiken, Hans
在HIV-1感染中，包括趋化因子(C-C基序)配体2(CCL2)在内的多种细胞因子和趋化因子被诱导。然而，HIV-1病毒血症对CCL2调节的影响在很大程度上是未知的。我们利用了覆盖110个炎症基因的DNA寡核苷酸微阵列。HIV-1病毒携带者(~gt；100.000个RNA拷贝m l(-1))的PBMC中有5个基因被至少2倍于无病毒者(<；50个RNA拷贝m l(-1))诱导。这些基因分别是CCL2、CXC趋化因子配体-10、干扰素-γ、GTP-环水解酶-1和C-C趋化因子受体-1。除了通过实时聚合酶链式反应验证微阵列数据外，对独立患者样本的分析显示了类似的表达模式。CCL2是基因表达水平上调控最强的基因，病毒血症组血清CCL2浓度明显高于病毒血症组和HIV-1血清阴性组，提示病毒血症与CCL2呈正相关。流式细胞仪研究显示，病毒携带者中表达CCL2的CD14+单核细胞比例高于无病毒携带者。这些结果表明HIV对宿主炎症基因反应的调节是高度受限的。在病毒感染状态下上调的基因，特别是CCL2，可能是HIV-1复制的潜在增强因素，表现为HIV-1病毒感染患者的高病毒载量。抑制增加的CCL2产生可能为HIV-1感染提供新的治疗干预措施。
Several cytokines and chemokines including chemokine (C-C motif) ligand-2 (CCL2) are induced in HIV-1 infection. However, the impact of HIV-1 viremia on CCL2 regulation is largely unknown. We utilized a DNA oligonucleotide microarray covering 110 inflammatory genes. Five genes were induced by at least 2-fold in PBMCs of HIV-1 viremic (> 100.000 RNA copies ml(-1)) as compared with aviremic (< 50 RNA copies ml(-1)) individuals. These genes were CCL2, CXC chemokine ligand-10, IFN-gamma, GTP-cyclohydrolase-1 and C-C chemokine receptor-1. In addition to microarray data verification by real-time PCR, analysis of independent patient samples revealed a similar expression pattern. CCL2 was the most strongly regulated gene at mRNA level and its serum concentration was significantly elevated in viremic compared with aviremic and HIV-1 seronegative controls, indicating a positive correlation between viremia and CCL2. Flow cytometric studies demonstrated a higher percentage of CCL2-expressing CD14+ monocytes in viremic compared with aviremic individuals. These results suggest a highly restricted modulation of host inflammatory gene response by HIV. Genes up-regulated in the viremic state, in particular CCL2, presumably serve as potential enhancing factors in HIV-1 replication, represented by high viral load in HIV-1 viremic patients. Inhibition of increased CCL2 production could provide a new therapeutic intervention in HIV-1 infection.