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Mycobacterium tuberculosis Induces Interleukin-32 Production through a Caspase- 1/IL-18/Interferon-γ-Dependent Mechanism
BACKGROUND: Interleukin (IL)–32 is a newly described proinflammatory cytokine that seems likely to play a role in inflammation and host defense. Little is known about the regulation of IL-32 production by primary cells of the immune system. METHODS AND FINDINGS: In the present study, freshly obtaine...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1539091/ https://www.ncbi.nlm.nih.gov/pubmed/16903774 http://dx.doi.org/10.1371/journal.pmed.0030277 |
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author | Netea, Mihai G Azam, Tania Lewis, Eli C Joosten, Leo A. B Wang, Maorong Langenberg, Dennis Meng, Xianzhong Chan, Edward D Yoon, Do-Young Ottenhoff, Tom Kim, Soo-Hyun Dinarello, Charles A |
author_facet | Netea, Mihai G Azam, Tania Lewis, Eli C Joosten, Leo A. B Wang, Maorong Langenberg, Dennis Meng, Xianzhong Chan, Edward D Yoon, Do-Young Ottenhoff, Tom Kim, Soo-Hyun Dinarello, Charles A |
author_sort | Netea, Mihai G |
collection | PubMed |
description | BACKGROUND: Interleukin (IL)–32 is a newly described proinflammatory cytokine that seems likely to play a role in inflammation and host defense. Little is known about the regulation of IL-32 production by primary cells of the immune system. METHODS AND FINDINGS: In the present study, freshly obtained human peripheral blood mononuclear cells were stimulated with different Toll-like receptor (TLR) agonists, and gene expression and synthesis of IL-32 was determined. We demonstrate that the TLR4 agonist lipopolysaccharide induces moderate (4-fold) production of IL-32, whereas agonists of TLR2, TLR3, TLR5, or TLR9, each of which strongly induced tumor necrosis factor α and IL-6, did not stimulate IL-32 production. However, the greatest amount of IL-32 was induced by the mycobacteria Mycobacterium tuberculosis and M. bovis BCG (20-fold over unstimulated cells). IL-32-induced synthesis by either lipopolysaccharide or mycobacteria remains entirely cell-associated in monocytes; moreover, steady-state mRNA levels are present in unstimulated monocytes without translation into IL-32 protein, similar to other cytokines lacking a signal peptide. IL-32 production induced by M. tuberculosis is dependent on endogenous interferon-γ (IFNγ); endogenous IFNγ is, in turn, dependent on M. tuberculosis–induced IL-18 via caspase-1. CONCLUSIONS: In conclusion, IL-32 is a cell-associated proinflammatory cytokine, which is specifically stimulated by mycobacteria through a caspase-1- and IL-18-dependent production of IFNγ. |
format | Text |
id | pubmed-1539091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-15390912006-09-18 Mycobacterium tuberculosis Induces Interleukin-32 Production through a Caspase- 1/IL-18/Interferon-γ-Dependent Mechanism Netea, Mihai G Azam, Tania Lewis, Eli C Joosten, Leo A. B Wang, Maorong Langenberg, Dennis Meng, Xianzhong Chan, Edward D Yoon, Do-Young Ottenhoff, Tom Kim, Soo-Hyun Dinarello, Charles A PLoS Med Research Article BACKGROUND: Interleukin (IL)–32 is a newly described proinflammatory cytokine that seems likely to play a role in inflammation and host defense. Little is known about the regulation of IL-32 production by primary cells of the immune system. METHODS AND FINDINGS: In the present study, freshly obtained human peripheral blood mononuclear cells were stimulated with different Toll-like receptor (TLR) agonists, and gene expression and synthesis of IL-32 was determined. We demonstrate that the TLR4 agonist lipopolysaccharide induces moderate (4-fold) production of IL-32, whereas agonists of TLR2, TLR3, TLR5, or TLR9, each of which strongly induced tumor necrosis factor α and IL-6, did not stimulate IL-32 production. However, the greatest amount of IL-32 was induced by the mycobacteria Mycobacterium tuberculosis and M. bovis BCG (20-fold over unstimulated cells). IL-32-induced synthesis by either lipopolysaccharide or mycobacteria remains entirely cell-associated in monocytes; moreover, steady-state mRNA levels are present in unstimulated monocytes without translation into IL-32 protein, similar to other cytokines lacking a signal peptide. IL-32 production induced by M. tuberculosis is dependent on endogenous interferon-γ (IFNγ); endogenous IFNγ is, in turn, dependent on M. tuberculosis–induced IL-18 via caspase-1. CONCLUSIONS: In conclusion, IL-32 is a cell-associated proinflammatory cytokine, which is specifically stimulated by mycobacteria through a caspase-1- and IL-18-dependent production of IFNγ. Public Library of Science 2006-08 2006-08-15 /pmc/articles/PMC1539091/ /pubmed/16903774 http://dx.doi.org/10.1371/journal.pmed.0030277 Text en © 2006 Netea et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Netea, Mihai G Azam, Tania Lewis, Eli C Joosten, Leo A. B Wang, Maorong Langenberg, Dennis Meng, Xianzhong Chan, Edward D Yoon, Do-Young Ottenhoff, Tom Kim, Soo-Hyun Dinarello, Charles A Mycobacterium tuberculosis Induces Interleukin-32 Production through a Caspase- 1/IL-18/Interferon-γ-Dependent Mechanism |
title |
Mycobacterium tuberculosis Induces Interleukin-32 Production through a Caspase- 1/IL-18/Interferon-γ-Dependent Mechanism |
title_full |
Mycobacterium tuberculosis Induces Interleukin-32 Production through a Caspase- 1/IL-18/Interferon-γ-Dependent Mechanism |
title_fullStr |
Mycobacterium tuberculosis Induces Interleukin-32 Production through a Caspase- 1/IL-18/Interferon-γ-Dependent Mechanism |
title_full_unstemmed |
Mycobacterium tuberculosis Induces Interleukin-32 Production through a Caspase- 1/IL-18/Interferon-γ-Dependent Mechanism |
title_short |
Mycobacterium tuberculosis Induces Interleukin-32 Production through a Caspase- 1/IL-18/Interferon-γ-Dependent Mechanism |
title_sort | mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/il-18/interferon-γ-dependent mechanism |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1539091/ https://www.ncbi.nlm.nih.gov/pubmed/16903774 http://dx.doi.org/10.1371/journal.pmed.0030277 |
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