Proinflammatory cytokines in the course of Mycobacterium tuberculosis-induced apoptosis in monocytes/macrophages.
J Infect Dis
; 186(9): 1277-82, 2002 Nov 01.
Article
in En
| MEDLINE
| ID: mdl-12402197
ABSTRACT
Mycobacterium tuberculosis (MTB) can induce apoptosis in monocytes/macrophages both in vitro and in vivo, and this phenomenon is associated with mycobacterial survival. The present study addresses the possibility that apoptotic and inflammatory pathways could coexist through a caspase-1-mediated mechanism. In this context, a caspase-1 inhibitor (YVAD), but not caspase-3 (DEVD) or caspase-4 (LEVD) inhibitors, was able to strongly inhibit MTB-induced apoptosis. Moreover, caspase-1 activity was confirmed by the increased maturation of interleukin (IL)-1beta. Of interest, IL-1beta and tumor necrosis factor (TNF)-alpha were produced massively in the course of infection, and both were inhibited by YVAD pretreatment. To determine whether TNF-alpha was produced actively by apoptotic cells, the intracytoplasmatic cytokine content and apoptotic phenotype were analyzed at the single-cell level. Results showed a progressive increase of TNF-alpha production in annexin V-positive cells. These results indicate that MTB-induced apoptosis is associated with proinflammatory cytokine production.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monocytes
/
Cytokines
/
Apoptosis
/
Macrophages
/
Mycobacterium tuberculosis
Limits:
Humans
Language:
En
Journal:
J Infect Dis
Year:
2002
Document type:
Article
Affiliation country:
Italy