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结核病中多巴胺和5-羟色胺基因受体的基因表达及体外药物遗传学研究

Gene Expression and In Vitro Pharmacogenetic Studies of Dopamine and Serotonin Gene Receptors in Tuberculosis.

作者信息

Sheikhpour Mojgan, Shokrgozar Mohammad Ali, Biglari Alireza, Pornour Majid, Abdolrahimi Farid, Poorazar Dizaji Shahin, Khanipour Sharareh, Masoumi Morteza, Ebrahimzadeh Nayereh, Abolfathi Hanieh

机构信息

Department of Mycobacteriology and Pulmonary Research, Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Zanjan University, Zanjan, Iran.

出版信息

Tanaffos. 2021 Feb;20(2):126-133.

Abstract

BACKGROUND

Dopamine and serotonin receptors are present in lymphocytes, macrophages, and neutrophils, and have a mediating role in the immune system to respond to infections, including bacterial tuberculosis.

MATERIALS AND METHODS

In this study, at first, the changes in the expression pattern of 5 dopamine and 2 serotonin (5HTR2B & 5HTR2C) gene receptors were examined in the two groups of healthy and Tuberculosis patients using Real-Time PCR. Then pharmacogenetic studies aimed to induce autophagy on a lung monocyte cell line (THP1) infected with the standard strain of (H37RV) were performed. Stimulation of the pro-inflammatory pathway by secreting cytokines before and after drug efficacy was investigated.

RESULTS

According to the result, dopamine receptor 2 genes showed decreased expression in patients with tuberculosis compared to normal individuals, and serotonin receptor genes showed increased expression. Additionally, with the effects of Bromocriptine and Fluoxetine, pro-inflammatory pathways were activated in macrophages infected with H37RV, and ELISA results showed that the levels of IL6 and TNFα secreted in these cells were significantly increased.

CONCLUSION

According to the results, these receptors agonists or antagonists can activate the autophagy pathway to kill TB bacteria.

摘要

背景

多巴胺和5-羟色胺受体存在于淋巴细胞、巨噬细胞和中性粒细胞中,在免疫系统对包括细菌性肺结核在内的感染作出反应中起介导作用。

材料与方法

在本研究中,首先,使用实时聚合酶链反应检测健康组和肺结核患者两组中5种多巴胺和2种5-羟色胺(5HTR2B和5HTR2C)基因受体表达模式的变化。然后进行药物遗传学研究,旨在对感染标准菌株(H37RV)的肺单核细胞系(THP1)诱导自噬。研究了药物疗效前后通过分泌细胞因子对促炎途径的刺激作用。

结果

结果显示,与正常个体相比,肺结核患者的多巴胺受体2基因表达降低,5-羟色胺受体基因表达增加。此外,在溴隐亭和氟西汀的作用下,感染H37RV的巨噬细胞中的促炎途径被激活,酶联免疫吸附测定结果显示这些细胞中分泌的白细胞介素6和肿瘤坏死因子α水平显著增加。

结论

根据结果,这些受体激动剂或拮抗剂可激活自噬途径以杀死结核杆菌。

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