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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Targeted deletion of cannabinoid receptors CB1 and CB2 produced enhanced inflammatory responses to influenza A/PR/8/34 in the absence and presence of Delta9-tetrahydrocannabinol.
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Targeted deletion of cannabinoid receptors CB1 and CB2 produced enhanced inflammatory responses to influenza A/PR/8/34 in the absence and presence of Delta9-tetrahydrocannabinol.

机译:在不存在和存在Delta9-四氢大麻酚的情况下,有针对性地删除大麻素受体CB1和CB2会增强对A / PR / 8/34流感的炎症反应。

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We have previously reported that Delta-9-tetrahydrocannabinol (Delta(9)-THC)-treated mice challenged with influenza virus A/PR/8/34 (PR8) developed increased viral hemagglutinin 1 (H1) mRNA levels and decreased monocyte and lymphocyte recruitment to the pulmonary airways when compared with mice challenged with PR8 alone. The objective of the present study was to examine the role of cannabinoid (CB(1)/CB(2)) receptors in mediating the effects of Delta(9)-THC on immune and epithelial cell responses to PR8. In the current study, Delta(9)-THC-treated CB(1)/CB(2) receptor null (CB(1)-/-/CB(2)-/-) and wild-type mice infected with PR8 had marked increases in viral H1 mRNA when compared with CB(1)-/-/CB(2)-/- and wild-type mice challenged with PR8 alone. However, the magnitude of the H1 mRNA levels was greatly reduced in CB(1)-/-/CB(2)-/- mice as compared with wild-type mice. In addition, Delta(9)-THC-treated CB(1)-/-/CB(2)-/- mice infected with PR8 had increased CD4+ T cells and IFN-gamma in bronchoalveolar lavage fluid with greater pulmonary inflammation when compared with Delta(9)-THC-treated wild-type mice infected with PR8. Delta(9)-THC treatment of CB(1)-/-/CB(2)-/- mice in the presence or absence of PR8 challenge also developed greater amounts of mucous cell metaplasia in the affected bronchiolar epithelium. Collectively, the immune and airway epithelial cell responses to PR8 challenge in Delta(9)-THC-treated CB(1)-/-/CB(2)-/- and wild-type mice indicated the involvement of CB(1)/CB(2) receptor-dependent and -independent mechanisms.
机译:我们以前曾报道过,用流感病毒A / PR / 8/34(PR8)攻击的Delta-9-四氢大麻酚(Delta(9)-THC)处理的小鼠发展了病毒血凝素1(H1)mRNA水平升高,单核细胞和淋巴细胞减少与仅接受PR8攻击的小鼠相比,肺征募入肺气道。本研究的目的是研究大麻素(CB(1)/ CB(2))受体在介导Delta(9)-THC对PR8的免疫和上皮细胞反应中的作用。在当前的研究中,经Delta(9)-THC处理的CB(1)/ CB(2)受体无效(CB(1)-/-// CB(2)-/-)和野生型小鼠感染了PR8与CB(1)-/-/ CB(2)-/-和仅用PR8攻击的野生型小鼠相比,病毒H1 mRNA的显着增加。但是,与野生型小鼠相比,CB(1)-/-// CB(2)-/-小鼠的H1 mRNA水平大大降低。此外,经Delta(9)-THC处理的CB(1)-/-// CB(2)-/-感染PR8的小鼠的支气管肺泡灌洗液中CD4 + T细胞和IFN-γ升高,与Delta(9)-THC处理的野生型小鼠感染PR8。在存在或不存在PR8攻击的情况下,对CB(1)-/-// CB(2)-/-小鼠进行Delta(9)-THC处理也可在受影响的细支气管上皮细胞中形成更多的粘液细胞化生。总体而言,Delta(9)-THC处理的CB(1)-/-// CB(2)-/-和野生型小鼠对PR8攻击的免疫和气道上皮细胞反应表明CB(1)/ CB(2)受体依赖性和非依赖性机制。

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