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Glibenclamide alters interleukin-8 and interleukin-1β of primary human monocytes from diabetes patients against Mycobacterium tuberculosis infection
Tuberculosis ( IF 3.2 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.tube.2020.101939
Chidchamai Kewcharoenwong 1 , Wipawee Saenwongsa 2 , Samuel J Willcocks 3 , Gregory J Bancroft 4 , Helen A Fletcher 4 , Ganjana Lertmemongkolchai 1
Affiliation  

Type 2 diabetes mellitus (T2DM) is an important risk factor for development of tuberculosis (TB). Our previous study showed glibenclamide, an anti-diabetic drug used to control blood glucose concentration, reduced interleukin (IL)-8 secretion from primary human monocytes challenged with M. tuberculosis (Mtb). In mice infected with Mtb, IL-1β is essential for host resistance through the enhancement of cyclooxygenase that limits excessive Type I interferon (IFN) production and fosters Mtb containment. We hypothesize that glibenclamide may also interfere with monocyte mediated immune responses against Mtb and alter the balance between IL-1β and IFNα-mediated immunity. Purified monocytes from non-diabetic and diabetic individuals were infected with Mtb or M. bovis BCG. We demonstrate that monocytes from diabetes patients who were being treated with glibenclamide showed reduced IL-1β and IL-8 secretion when exposed to Mtb. Additionally, these responses also occurred when monocytes from non-diabetic individuals were pre-treated with glibenclamide in vitro. Moreover, this pre-treatment enhanced IFNa1 expression but was not involved with prostaglandin E2 (PGE2) expression in response to Mtb infection. Taken together, our data show that glibenclamide might exacerbate susceptibility of diabetes patients to Mtb infection by reducing IL-1β and IL-8 production by monocytes.

中文翻译:

格列本脲改变糖尿病患者原代人单核细胞的白细胞介素8和白细胞介素1β对抗结核分枝杆菌感染

2 型糖尿病 (T2DM) 是结核病 (TB) 发展的重要危险因素。我们之前的研究表明,格列本脲是一种用于控制血糖浓度的抗糖尿病药物,可减少受结核分枝杆菌 (Mtb) 攻击的原代人类单核细胞的白介素 (IL)-8 分泌。在感染 Mtb 的小鼠中,IL-1β 通过增强环加氧酶来限制过多的 I 型干扰素 (IFN) 产生并促进 Mtb 遏制,从而对宿主抵抗力至关重要。我们假设格列本脲还可能干扰单核细胞介导的针对 Mtb 的免疫反应,并改变 IL-1β 和 IFNα 介导的免疫之间的平衡。来自非糖尿病和糖尿病个体的纯化单核细胞被 Mtb 或牛分枝杆菌 BCG 感染。我们证明,接受格列本脲治疗的糖尿病患者的单核细胞在暴露于 Mtb 时显示出 IL-1β 和 IL-8 分泌减少。此外,当非糖尿病个体的单核细胞在体外用格列本脲预处理时也会发生这些反应。此外,这种预处理增强了 IFNa1 表达,但不参与响应 Mtb 感染的前列腺素 E2 (PGE2) 表达。总之,我们的数据表明格列本脲可能通过减少单核细胞产生 IL-1β 和 IL-8 来加剧糖尿病患者对 Mtb 感染的易感性。这种预处理增强了 IFNa1 表达,但不参与响应 Mtb 感染的前列腺素 E2 (PGE2) 表达。总之,我们的数据表明格列本脲可能通过减少单核细胞产生 IL-1β 和 IL-8 来加剧糖尿病患者对 Mtb 感染的易感性。这种预处理增强了 IFNa1 表达,但不参与响应 Mtb 感染的前列腺素 E2 (PGE2) 表达。总之,我们的数据表明格列本脲可能通过减少单核细胞产生 IL-1β 和 IL-8 来加剧糖尿病患者对 Mtb 感染的易感性。
更新日期:2020-07-01
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