Rosas-Taraco Adrian G, Higgins David M, Sánchez-Campillo Joaquín, Lee Eric J, Orme Ian M, González-Juarrero Mercedes
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA.
Am J Respir Cell Mol Biol. 2009 Aug;41(2):136-45. doi: 10.1165/rcmb.2008-0363OC. Epub 2008 Dec 18.
Mice infected for 60 days with Mycobacterium tuberculosis were treated with aerosolized XCL1-targeting small interfering RNA (siRNA) to induce local and transient suppression of XCL1/lymphotactin (an important chemokine in tuberculoid granuloma formation). The local pulmonary siRNA therapy resulted in a 50% decrease in the total amount of xcl1 gene transcripts at 3 days, and 40 to 50% protein suppression 3 and 5 days after treatment. Reduced XCL1 expression in the lungs was associated with decreased numbers of T lymphocytes, reduction in the IFN-gamma response, disorganized granulomatous lesions, and higher fibrosis when compared with control mice treated with either PBS or nontargeting siRNA. This indicates that a transient but strong modulation of the production of XCL1 in the lungs has a significant effect on the influx of IFN-gamma-secreting T cells, as well as local pathology, but without significantly altering containment of the infection.
用雾化的靶向XCL1的小干扰RNA（siRNA）对感染结核分枝杆菌60天的小鼠进行治疗，以诱导XCL1/淋巴细胞趋化因子（结核样肉芽肿形成中的一种重要趋化因子）的局部和短暂抑制。局部肺部siRNA治疗导致3天时xcl1基因转录本总量减少50%，治疗后3天和5天蛋白质抑制率为40%至50%。与用PBS或非靶向siRNA治疗的对照小鼠相比，肺中XCL1表达降低与T淋巴细胞数量减少、IFN-γ反应降低、肉芽肿病变紊乱和更高的纤维化有关。这表明肺中XCL1产生的短暂但强烈的调节对分泌IFN-γ的T细胞流入以及局部病理有显著影响，但不会显著改变感染的控制。
