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| 購買進口儀器、試劑和耗材——就在始于2001年的畢特博生物 www.pyjb.com.cn |
英國研究人員日前報告說，他們對肺結核發病過程中肺部組織受損的原因有了新認識，一種酶被發現在其中發揮關鍵作用，因此可以通過抑制這種酶的作用來治療肺結核。這一發現可能會很快轉化為實際療法。 英國帝國理工學院的研究人員在美國新一期《臨床研究期刊》上報告說，他們對一些肺結核患者的檢查顯示，患者體內一種名為MMP-1的酶含量較高。研究人員隨后在試管中培養了人體細胞，讓其感染結核桿菌，結果也發現，其中的這種酶含量上升。研究人員還開展了動物實驗，結果顯示在實驗鼠體內，這種酶含量上升會導致與人類患者相似的肺部受損情況。 研究人員認為，如果能夠用藥物抑制這種酶的作用，也許可以成為治療肺結核的新途徑。本次研究已經證實，對在試管中培養的感染了結核桿菌的人體細胞而言，能夠使用一些已有的藥物來抑制這種酶的作用。 研究人員保羅·埃爾金頓說，肺結核的療法近幾十年來沒有太大進展，本次研究揭示了一種新的治療途徑，尤其重要的是，也許可以使用一些現有的藥物。 肺結核是由結核桿菌引起的傳染病，癥狀表現為經常咳嗽、疲倦乏力等，嚴重者會咯血甚至死亡，在歷史上曾長期被認為是不治之癥。20世紀相關抗生素問世后，肺結核的治療變得較容易，但隨著細菌耐藥性的逐漸增強，肺結核在全球有卷土重來的趨勢。 推薦原文出處： J Clin Invest. doi:10.1172/JCI45666. MMP-1 drives immunopathology in human tuberculosis and transgenic mice Paul Elkington1, Takayuki Shiomi2, Ronan Breen3, Robert K. Nuttall4, Cesar Augusto Ugarte-Gil1, Naomi F. Walker1, Luísa Saraiva1, Bernadette Pedersen1, Francesco Mauri5, Marc Lipman3, Dylan R. Edwards4, Brian D. Robertson6, Jeanine D’Armiento2 and Jon S. Friedland1 Mycobacterium tuberculosis can cause lung tissue damage to spread, but the mechanisms driving this immunopathology are poorly understood. The breakdown of lung matrix involves MMPs, which have a unique ability to degrade fibrillar collagens at neutral pH. To determine whether MMPs play a role in the immunopathology of tuberculosis (TB), we profiled MMPs and their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs), in sputum and bronchoalveolar lavage fluid from patients with TB and symptomatic controls. MMP-1 concentrations were significantly increased in both HIV-negative and HIV-positive patients with TB, while TIMP concentrations were lower in HIV-negative TB patients. In primary human monocytes, M. tuberculosis infection selectively upregulated MMP1 gene expression and secretion, and Ro32-3555, a specific MMP inhibitor, suppressed M. tuberculosis–driven MMP-1 activity. Since the mouse MMP-1 ortholog is not expressed in the lung and mice infected with M. tuberculosis do not develop tissue destruction equivalent to humans, we infected transgenic mice expressing human MMP-1 with M. tuberculosis to investigate whether MMP-1 caused lung immunopathology. In the MMP-1 transgenic mice, M. tuberculosis infection increased MMP-1 expression, resulting in alveolar destruction in lung granulomas and significantly greater collagen breakdown. In summary, MMP-1 may drive tissue destruction in TB and represents a therapeutic target to limit immunopathology.
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購買進口儀器、試劑和耗材——就在始于2001年的畢特博生物
www.pyjb.com.cn |
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