Aerosolized gamma interferon (IFN-γ) induces expression of the genes encoding the IFN-γ-inducible 10-kilodalton protein but not inducible nitric oxide synthase in the lung during tuberculosis
Aerosolized gamma interferon (IFN-γ) induces expression of the genes encoding the IFN-γ-inducible 10-kilodalton protein but not inducible nitric oxide synthase in the lung during tuberculosis
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DOI：
10.1128/iai.72.3.1275-1283.2004
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发表时间：
2004-03-01
影响因子：
3.1
通讯作者：
Weiden, MD
中科院分区：
文献类型：
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作者：
Raju, B;Hoshino, Y;Weiden, MD
γ干扰素（ifn - γ）在对抗结核分枝杆菌的免疫应答中起关键作用。在一项正在进行的气溶胶IFN- γ联合标准药物治疗的试验中，我们观察到结核（TB）患者支气管肺泡灌洗（BAL）细胞中IFN信号的激活。我们假设气溶胶ifn - γ治疗肺结核会增加控制肺结核的重要基因的表达。我们通过实时定量逆转录pcr检测诱导型一氧化氮合酶（MOS）和趋化因子ifn诱导型10-kDa蛋白（IP-10）的下游基因表达情况。体外，结核分枝杆菌诱导IP-10， ifn - γ进一步刺激IP-10，但对MOS表达无影响。我们研究了21例肺结核患者和7名健康者。与体外模型类似，IP-10 mRNA在TB患者BAL细胞中升高，并在雾化ifn - γ治疗后增强。结核也与MOS mRNA升高有关，但雾化ifn - γ并没有进一步增强表达。基因组分析鉴定了6名结核病患者在治疗前后1个月的BAL细胞中表达的4058个基因中的1300个，包括雾化ifn - γ。然而，只有15个基因受到ifn - γ的差异调节。我们得出结论，iNOS和IP-10 mRNA在结核病中表达增加，但气溶胶ifn - γ治疗增加了人肺中少数基因的表达。
Gamma interferon (IFN-gamma) is critical in the immune response against Mycobacterium tuberculosis. In an ongoing trial of aerosol IFN-gamma in conjunction with standard drug therapy, we have observed activation of IFN signaling in bronchoalveolar lavage (BAL) cells from tuberculosis (TB) patients. We hypothesized that aerosol IFN-gamma treatment of pulmonary TB would increase expression of genes important for the control of TB. We investigated the expression of downstream genes by measuring inducible nitric oxide synthase (MOS) and the chemokine IFN-inducible 10-kDa protein (IP-10) by real-time quantitative reverse transcription-PCR. In vitro, M. tuberculosis induced IP-10, and IFN-gamma stimulated this further, with no effect on MOS expression. We studied 21 patients with pulmonary TB and 7 healthy subjects. Similar to the in vitro model, IP-10 mRNA was increased in BAL cells from TB patients and was augmented after treatment with aerosolized IFN-gamma. TB was also associated with elevated MOS mRNA, but aerosolized IFN-gamma did not further enhance expression. Genomic analysis identified 1,300 of 4,058 genes expressed in BAL cells from six TB patients before and after I month of therapy, including aerosolized IFN-gamma. However, only 15 genes were differentially regulated by IFN-gamma. We conclude that iNOS and IP-10 mRNA expression is increased in TB but that aerosol IFN-gamma treatment increases expression of few genes in the human lung.