Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/20169
HEME OXYGENASE-1 REGULATION OF MATRIX METALLOPROTEINASE-1 EXPRESSION UNDERLIES DISTINCT DISEASE PROFILES IN TUBERCULOSIS
Matrix Metalloproteinase 1
Heme Oxygenase-1
Mycobacterium tuberculosis
Macrófagos
Biomarcadores
Humanos
Adulto
Matrix Metalloproteinase 1
Heme Oxygenase-1
Mycobacterium tuberculosis
Macrophages
Biomarkers
Humans
Adult
Oxidative Stress
Estresse oxidativo
Author
Andrade, Bruno de Bezerril
Pavan Kumar, Nathella
Amaral, Eduardo Pinheiro
Riteau, Nicolas
Mayer-Barber, Katrin D
Tosh, Kevin W
Maier, Nolan
Conceição, Elisabete Lopes
Kubler, Andre
Sridhar, Rathinam
Banurekha, Vaithilingam V
Jawahar, Mohideen S
Bessa, Theolis Costa Barbosa
Manganiello, Vincent C
Moss, Joel
Fontana, Joseph R
Marciano, Beatriz E
Sampaio, Elizabeth P
Olivier, Kenneth N
Holland, Steven M
Jackson, Sharon H
Moayeri, Mahtab
Leppla, Stephen
Sereti, Irini
Barber, Daniel L
Nutman, Thomas B
Babu, Subash
Sher, Alan
Pavan Kumar, Nathella
Amaral, Eduardo Pinheiro
Riteau, Nicolas
Mayer-Barber, Katrin D
Tosh, Kevin W
Maier, Nolan
Conceição, Elisabete Lopes
Kubler, Andre
Sridhar, Rathinam
Banurekha, Vaithilingam V
Jawahar, Mohideen S
Bessa, Theolis Costa Barbosa
Manganiello, Vincent C
Moss, Joel
Fontana, Joseph R
Marciano, Beatriz E
Sampaio, Elizabeth P
Olivier, Kenneth N
Holland, Steven M
Jackson, Sharon H
Moayeri, Mahtab
Leppla, Stephen
Sereti, Irini
Barber, Daniel L
Nutman, Thomas B
Babu, Subash
Sher, Alan
Affilliation
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Unidade de Medicina Investigativa. Laboratório Integrado de Microbiologia e Imunorregulação. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Unidade de Medicina Investigativa. Laboratório Integrado de Microbiologia e Imunorregulação. Salvador, BA, Brasil
Múltipla – ver em Notas
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Unidade de Medicina Investigativa. Laboratório Integrado de Microbiologia e Imunorregulação. Salvador, BA, Brasil
Múltipla – ver em Notas
Abstract
Pulmonary tuberculosis (TB) is characterized by oxidative stress and lung tissue destruction by matrix metalloproteinases (MMPs). The interplay between these distinct pathological processes and the implications for TB diagnosis and disease staging are poorly understood. Heme oxygenase-1 (HO-1) levels were previously shown to distinguish active from latent TB, as well as successfully treated Mycobacterium tuberculosis infection. MMP-1 expression is also associated with active TB. In this study, we measured plasma levels of these two important biomarkers in distinct TB cohorts from India and Brazil. Patients with active TB expressed either very high levels of HO-1 and low levels of MMP-1 or the converse. Moreover, TB patients with either high HO-1 or MMP-1 levels displayed distinct clinical presentations, as well as plasma inflammatory marker profiles. In contrast, in an exploratory North American study, inversely correlated expression of HO-1 and MMP-1 was not observed in patients with other nontuberculous lung diseases. To assess possible regulatory interactions in the biosynthesis of these two enzymes at the cellular level, we studied the expression of HO-1 and MMP-1 in M. tuberculosis-infected human and murine macrophages. We found that infection of macrophages with live virulent M. tuberculosis is required for robust induction of high levels of HO-1 but not MMP-1. In addition, we observed that CO, a product of M. tuberculosis-induced HO-1 activity, inhibits MMP-1 expression by suppressing c-Jun/AP-1 activation. These findings reveal a mechanistic link between oxidative stress and tissue remodeling that may find applicability in the clinical staging of TB patients.
Keywords in Portuguese
Tuberculose, PulmonarMatrix Metalloproteinase 1
Heme Oxygenase-1
Mycobacterium tuberculosis
Macrófagos
Biomarcadores
Humanos
Adulto
Keywords
Tuberculosis, PulmonaryMatrix Metalloproteinase 1
Heme Oxygenase-1
Mycobacterium tuberculosis
Macrophages
Biomarkers
Humans
Adult
Oxidative Stress
Estresse oxidativo
Share