Inhibitory Effects of Dutasteride on TLR4: An In vitro Pain Study

Dutasteride was potentially proposed to control chronic pain by Toll-Like Receptor 4 (TLR4) inhibition through its effect on TLR4 expression, Myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), secretory Interleukin-1β (IL-1β)...

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Main Authors: Leila Taheran, Hakimeh Zali, Kazem Sharifi, Mohsen Yazdani, Mohammad Ajoudanian, Mir-Shahram Safari, Samira Rajaei, Ali Dabbagh
Format: Article
Language:English
Published: Tehran University of Medical Sciences 2022-10-01
Series:Iranian Journal of Allergy, Asthma and Immunology
Subjects:
Online Access:https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3547
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author Leila Taheran
Hakimeh Zali
Kazem Sharifi
Mohsen Yazdani
Mohammad Ajoudanian
Mir-Shahram Safari
Samira Rajaei
Ali Dabbagh
author_facet Leila Taheran
Hakimeh Zali
Kazem Sharifi
Mohsen Yazdani
Mohammad Ajoudanian
Mir-Shahram Safari
Samira Rajaei
Ali Dabbagh
author_sort Leila Taheran
collection DOAJ
description Dutasteride was potentially proposed to control chronic pain by Toll-Like Receptor 4 (TLR4) inhibition through its effect on TLR4 expression, Myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), secretory Interleukin-1β (IL-1β), and nitric oxide (NO) in the Lipopolysaccharides (LPS)-stimulated U-87 MG cell line. Human astrocytoma U-87 MG cell line was cultured and incubated with 10 μg/mL of LPS for 24 hours to create a neuro-inflammation model, using two different treatment approaches. The first approach included LPS treatment for 24 hours, followed by dutasteride (20 μg/mL) incubation for the next 72 hours. In the second treatment approach, the cells were co-incubated with LPS and dutasteride for 72 hours. Expression of TLR4, MyD88, NF-κBp65, and secretory IL-1 was evaluated by Western blotting while expression of NO was assessed by NO assay. TLR4, MyD88, NF-κBp65, and secretory IL-1β levels increased in LPS-treated cells after 24 hours. Dutasteride significantly decreased the secretion of NO and also, the levels of TLR4, MyD88, and NF-κBp65 in both treatment approaches. No difference in IL-1β level was seen with the second treatment approach. Dutasteride has anti-inflammatory properties and probably analgesic effects, by mechanisms different from conventional analgesics.
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spelling doaj.art-e1f6660d9a6a421b95799472d99b82ac2022-12-22T03:03:36ZengTehran University of Medical SciencesIranian Journal of Allergy, Asthma and Immunology1735-15021735-52492022-10-0121510.18502/ijaai.v21i5.11044Inhibitory Effects of Dutasteride on TLR4: An In vitro Pain StudyLeila Taheran0Hakimeh Zali1Kazem Sharifi2Mohsen Yazdani3Mohammad Ajoudanian4Mir-Shahram Safari5Samira Rajaei6Ali Dabbagh7Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Tissue Engineering, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, IranDepartment of Medical Nanotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranNeuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranAnesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Department of Anesthesiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Dutasteride was potentially proposed to control chronic pain by Toll-Like Receptor 4 (TLR4) inhibition through its effect on TLR4 expression, Myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), secretory Interleukin-1β (IL-1β), and nitric oxide (NO) in the Lipopolysaccharides (LPS)-stimulated U-87 MG cell line. Human astrocytoma U-87 MG cell line was cultured and incubated with 10 μg/mL of LPS for 24 hours to create a neuro-inflammation model, using two different treatment approaches. The first approach included LPS treatment for 24 hours, followed by dutasteride (20 μg/mL) incubation for the next 72 hours. In the second treatment approach, the cells were co-incubated with LPS and dutasteride for 72 hours. Expression of TLR4, MyD88, NF-κBp65, and secretory IL-1 was evaluated by Western blotting while expression of NO was assessed by NO assay. TLR4, MyD88, NF-κBp65, and secretory IL-1β levels increased in LPS-treated cells after 24 hours. Dutasteride significantly decreased the secretion of NO and also, the levels of TLR4, MyD88, and NF-κBp65 in both treatment approaches. No difference in IL-1β level was seen with the second treatment approach. Dutasteride has anti-inflammatory properties and probably analgesic effects, by mechanisms different from conventional analgesics. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3547DutasterideNeuropathic painToll-like receptor 4
spellingShingle Leila Taheran
Hakimeh Zali
Kazem Sharifi
Mohsen Yazdani
Mohammad Ajoudanian
Mir-Shahram Safari
Samira Rajaei
Ali Dabbagh
Inhibitory Effects of Dutasteride on TLR4: An In vitro Pain Study
Iranian Journal of Allergy, Asthma and Immunology
Dutasteride
Neuropathic pain
Toll-like receptor 4
title Inhibitory Effects of Dutasteride on TLR4: An In vitro Pain Study
title_full Inhibitory Effects of Dutasteride on TLR4: An In vitro Pain Study
title_fullStr Inhibitory Effects of Dutasteride on TLR4: An In vitro Pain Study
title_full_unstemmed Inhibitory Effects of Dutasteride on TLR4: An In vitro Pain Study
title_short Inhibitory Effects of Dutasteride on TLR4: An In vitro Pain Study
title_sort inhibitory effects of dutasteride on tlr4 an in vitro pain study
topic Dutasteride
Neuropathic pain
Toll-like receptor 4
url https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3547
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