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

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

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

Document Type : Original Article

Authors

Mojgan Sheikhpour ¹

Mohammad Ali Shokrgozar ²

Alireza Biglari ³

Majid Pornour ⁴

Farid Abdolrahimi ¹

Shahin Poorazar Dizaji ¹

Sharareh Khanipour ¹

Morteza Masoumi ¹

Nayereh Ebrahimzadeh ¹

Hanieh Abolfathi ¹

¹ Department of Mycobacteriology and Pulmonary Research, Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran

² Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Zanjan University, Zanjan, Iran

³ National Cell Bank, Pasteur Institute of Iran, Tehran, Iran

⁴ Photo Healing and Regeneration Research Group, Medical Laser Research Center, ACECR, Tehran, Iran

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 Mycobacterium tuberculosis (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.

Keywords

Dopamine receptors

Serotonin receptors, Mycobacterium tuberculosis

Cytokines

Autophagy