Cargando…
The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages
Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance a...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242622/ https://www.ncbi.nlm.nih.gov/pubmed/28111615 http://dx.doi.org/10.1016/j.jcte.2016.08.005 |
_version_ | 1782496365667942400 |
---|---|
author | Chesdachai, Supavit Zughaier, Susu M. Hao, Li Kempker, Russell R. Blumberg, Henry M. Ziegler, Thomas R. Tangpricha, Vin |
author_facet | Chesdachai, Supavit Zughaier, Susu M. Hao, Li Kempker, Russell R. Blumberg, Henry M. Ziegler, Thomas R. Tangpricha, Vin |
author_sort | Chesdachai, Supavit |
collection | PubMed |
description | Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance are uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages. To address this hypothesis, human macrophage-like monocytic (THP-1) cells were treated with varying doses of first-line anti-tuberculosis drugs in the presence of the active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). The expression of hCAP18 was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 1,25(OH)(2)D(3) strongly induced expression of hCAP18 mRNA in THP-1 cells (fold-change from control). The combination of the standard 4-drug TB therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) in the cultured THP-1 cells demonstrated a significant decrease in hCAP18 mRNA at the dosage of 10 µg/mL. In 31 subjects with newly diagnosed drug-sensitive TB randomized to either high-dose vitamin D(3) (1.2 million IU over 8 weeks, n = 13) versus placebo (n = 18), there was no change from baseline to week 8 in hCAP18 mRNA levels in peripheral blood mononuclear cells or in plasma concentrations of LL-37, the protein product of hCAP18. These data suggest that first-line anti-TB drugs may alter the vitamin D-dependent increase in hCAP18 and LL-37 human macrophages. |
format | Online Article Text |
id | pubmed-5242622 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-52426222017-10-24 The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages Chesdachai, Supavit Zughaier, Susu M. Hao, Li Kempker, Russell R. Blumberg, Henry M. Ziegler, Thomas R. Tangpricha, Vin J Clin Transl Endocrinol Research Paper Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance are uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages. To address this hypothesis, human macrophage-like monocytic (THP-1) cells were treated with varying doses of first-line anti-tuberculosis drugs in the presence of the active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). The expression of hCAP18 was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 1,25(OH)(2)D(3) strongly induced expression of hCAP18 mRNA in THP-1 cells (fold-change from control). The combination of the standard 4-drug TB therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) in the cultured THP-1 cells demonstrated a significant decrease in hCAP18 mRNA at the dosage of 10 µg/mL. In 31 subjects with newly diagnosed drug-sensitive TB randomized to either high-dose vitamin D(3) (1.2 million IU over 8 weeks, n = 13) versus placebo (n = 18), there was no change from baseline to week 8 in hCAP18 mRNA levels in peripheral blood mononuclear cells or in plasma concentrations of LL-37, the protein product of hCAP18. These data suggest that first-line anti-TB drugs may alter the vitamin D-dependent increase in hCAP18 and LL-37 human macrophages. Elsevier 2016-09-14 /pmc/articles/PMC5242622/ /pubmed/28111615 http://dx.doi.org/10.1016/j.jcte.2016.08.005 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Chesdachai, Supavit Zughaier, Susu M. Hao, Li Kempker, Russell R. Blumberg, Henry M. Ziegler, Thomas R. Tangpricha, Vin The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages |
title | The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages |
title_full | The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages |
title_fullStr | The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages |
title_full_unstemmed | The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages |
title_short | The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages |
title_sort | effects of first-line anti-tuberculosis drugs on the actions of vitamin d in human macrophages |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242622/ https://www.ncbi.nlm.nih.gov/pubmed/28111615 http://dx.doi.org/10.1016/j.jcte.2016.08.005 |
work_keys_str_mv | AT chesdachaisupavit theeffectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT zughaiersusum theeffectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT haoli theeffectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT kempkerrussellr theeffectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT blumberghenrym theeffectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT zieglerthomasr theeffectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT tangprichavin theeffectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT chesdachaisupavit effectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT zughaiersusum effectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT haoli effectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT kempkerrussellr effectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT blumberghenrym effectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT zieglerthomasr effectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages AT tangprichavin effectsoffirstlineantituberculosisdrugsontheactionsofvitamindinhumanmacrophages |