Drug repositioning identifies histone deacetylase inhibitors that promote innate immunity in non-tuberculous mycobacterial infection.
Can J Microbiol
; 70(7): 252-261, 2024 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-38855942
ABSTRACT
Non-tuberculosis infections in immunocompromised patients represent a cause for concern, given the increased risks of infection, and limited treatments available. Herein, we report that molecules for binding to the catalytic site of histone deacetylase (HDAC) inhibit its activity, thus increasing the innate immune response against environmental mycobacteria. The action of HDAC inhibitors (iHDACs) was explored in a model of type II pneumocytes and macrophages infection by Mycobacterium aurum. The results show that the use of 1,3-diphenylurea increases the expression of the TLR-4 in M. aurum infected MDMs, as well as the production of defb4, IL-1ß, IL-12, and IL-6. Moreover, we observed that aminoacetanilide upregulates the expression of TLR-4 together with TLR-9, defb4, CAMP, RNase 6, RNase 7, IL-1ß, IL-12, and IL-6 in T2P. Results conclude that the tested iHDACs selectively modulate the expression of cytokines and antimicrobial peptides that are associated with reduction of non-tuberculous mycobacteria infection.
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Base de dados:
MEDLINE
Assunto principal:
Citocinas
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Inibidores de Histona Desacetilases
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Reposicionamento de Medicamentos
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Imunidade Inata
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Infecções por Mycobacterium não Tuberculosas
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article