Cargando…
Nitric Oxide Synthesis is Modulated by 1,25-Dihydroxyvitamin D3 and Interferon-γ in Human Macrophages after Mycobacterial Infection
BACKGROUND: Little information is available the role of Nitric Oxide (NO) in host defenses during human tuberculosis (TB) infection. We investigated the modulating factor(s) affecting NO synthase (iNOS) induction in human macrophages. METHODS: Both iNOS mRNA and protein that regulate the growth of m...
Autores principales: | , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Korean Association of Immunologists
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816953/ https://www.ncbi.nlm.nih.gov/pubmed/20157607 http://dx.doi.org/10.4110/in.2009.9.5.192 |
_version_ | 1782177159485325312 |
---|---|
author | Lee, Ji-Sook Yang, Chul-Su Shin, Dong-Min Yuk, Jae-Min Son, Ji-Woong Jo, Eun-Kyeong |
author_facet | Lee, Ji-Sook Yang, Chul-Su Shin, Dong-Min Yuk, Jae-Min Son, Ji-Woong Jo, Eun-Kyeong |
author_sort | Lee, Ji-Sook |
collection | PubMed |
description | BACKGROUND: Little information is available the role of Nitric Oxide (NO) in host defenses during human tuberculosis (TB) infection. We investigated the modulating factor(s) affecting NO synthase (iNOS) induction in human macrophages. METHODS: Both iNOS mRNA and protein that regulate the growth of mycobacteria were determined using reverase transcriptase-polymerase chain reaction and western blot analysis. The upstream signaling pathways were further investigated using iNOS specific inhibitors. RESULTS: Here we show that combined treatment with 1,25-dihydroxyvitamin D3 (1,25-D3) and Interferon (IFN)-γ synergistically enhanced NO synthesis and iNOS expression induced by Mycobacterium tuberculosis (MTB) or by its purified protein derivatives in human monocyte-derived macrophages. Both the nuclear factor-κB and MEK1-ERK1/2 pathways were indispensable in the induction of iNOS expression, as shown in toll like receptor 2 stimulation. Further, the combined treatment with 1,25-D3 and IFN-γ was more potent than either agent alone in the inhibition of intracellular MTB growth. Notably, this enhanced effect was not explained by increased expression of cathelicidin, a known antimycobacterial effector of 1,25-D3. CONCLUSION: These data support a key role of NO in host defenses against TB and identify novel modulating factors for iNOS induction in human macrophages. |
format | Text |
id | pubmed-2816953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Korean Association of Immunologists |
record_format | MEDLINE/PubMed |
spelling | pubmed-28169532010-02-12 Nitric Oxide Synthesis is Modulated by 1,25-Dihydroxyvitamin D3 and Interferon-γ in Human Macrophages after Mycobacterial Infection Lee, Ji-Sook Yang, Chul-Su Shin, Dong-Min Yuk, Jae-Min Son, Ji-Woong Jo, Eun-Kyeong Immune Netw Original Article BACKGROUND: Little information is available the role of Nitric Oxide (NO) in host defenses during human tuberculosis (TB) infection. We investigated the modulating factor(s) affecting NO synthase (iNOS) induction in human macrophages. METHODS: Both iNOS mRNA and protein that regulate the growth of mycobacteria were determined using reverase transcriptase-polymerase chain reaction and western blot analysis. The upstream signaling pathways were further investigated using iNOS specific inhibitors. RESULTS: Here we show that combined treatment with 1,25-dihydroxyvitamin D3 (1,25-D3) and Interferon (IFN)-γ synergistically enhanced NO synthesis and iNOS expression induced by Mycobacterium tuberculosis (MTB) or by its purified protein derivatives in human monocyte-derived macrophages. Both the nuclear factor-κB and MEK1-ERK1/2 pathways were indispensable in the induction of iNOS expression, as shown in toll like receptor 2 stimulation. Further, the combined treatment with 1,25-D3 and IFN-γ was more potent than either agent alone in the inhibition of intracellular MTB growth. Notably, this enhanced effect was not explained by increased expression of cathelicidin, a known antimycobacterial effector of 1,25-D3. CONCLUSION: These data support a key role of NO in host defenses against TB and identify novel modulating factors for iNOS induction in human macrophages. The Korean Association of Immunologists 2009-10 2009-10-30 /pmc/articles/PMC2816953/ /pubmed/20157607 http://dx.doi.org/10.4110/in.2009.9.5.192 Text en Copyright © 2009 The Korean Association of Immunologists http://creativecommons.org/licenses/by-nc/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Lee, Ji-Sook Yang, Chul-Su Shin, Dong-Min Yuk, Jae-Min Son, Ji-Woong Jo, Eun-Kyeong Nitric Oxide Synthesis is Modulated by 1,25-Dihydroxyvitamin D3 and Interferon-γ in Human Macrophages after Mycobacterial Infection |
title | Nitric Oxide Synthesis is Modulated by 1,25-Dihydroxyvitamin D3 and Interferon-γ in Human Macrophages after Mycobacterial Infection |
title_full | Nitric Oxide Synthesis is Modulated by 1,25-Dihydroxyvitamin D3 and Interferon-γ in Human Macrophages after Mycobacterial Infection |
title_fullStr | Nitric Oxide Synthesis is Modulated by 1,25-Dihydroxyvitamin D3 and Interferon-γ in Human Macrophages after Mycobacterial Infection |
title_full_unstemmed | Nitric Oxide Synthesis is Modulated by 1,25-Dihydroxyvitamin D3 and Interferon-γ in Human Macrophages after Mycobacterial Infection |
title_short | Nitric Oxide Synthesis is Modulated by 1,25-Dihydroxyvitamin D3 and Interferon-γ in Human Macrophages after Mycobacterial Infection |
title_sort | nitric oxide synthesis is modulated by 1,25-dihydroxyvitamin d3 and interferon-γ in human macrophages after mycobacterial infection |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816953/ https://www.ncbi.nlm.nih.gov/pubmed/20157607 http://dx.doi.org/10.4110/in.2009.9.5.192 |
work_keys_str_mv | AT leejisook nitricoxidesynthesisismodulatedby125dihydroxyvitamind3andinterferonginhumanmacrophagesaftermycobacterialinfection AT yangchulsu nitricoxidesynthesisismodulatedby125dihydroxyvitamind3andinterferonginhumanmacrophagesaftermycobacterialinfection AT shindongmin nitricoxidesynthesisismodulatedby125dihydroxyvitamind3andinterferonginhumanmacrophagesaftermycobacterialinfection AT yukjaemin nitricoxidesynthesisismodulatedby125dihydroxyvitamind3andinterferonginhumanmacrophagesaftermycobacterialinfection AT sonjiwoong nitricoxidesynthesisismodulatedby125dihydroxyvitamind3andinterferonginhumanmacrophagesaftermycobacterialinfection AT joeunkyeong nitricoxidesynthesisismodulatedby125dihydroxyvitamind3andinterferonginhumanmacrophagesaftermycobacterialinfection |