Apoptosis modulation by mycolic acid, tuberculostearic acid and trehalose 6,6'-dimycolate.
The object of our study is to demonstrate that some components of M. tuberculosis, such as cord factor or mycolic acid or whole bacteria can prolong cell survival compared to controls. The cells treated with cord factor or mycolic acid at a concentration of 5 microg/ml were 65+/-8% viable reaching 70+/-8% at a concentration of 10 microg/ml. The cells treated with heat killed mycobacteria were 70+/-8% viable; while control cells exhibited a viability 50+/-7%. Conversely, tuberculostearic acid induced early cell death. The results also demonstrated a dose-dependent effect on the viability or induction of macrophage apoptosis. We also showed that prolonged viability of the treated cells with mycolic acid or cord factor (+20+/-4% and +25+/-5%, respectively) was correlated with a significant increase in Bcl-2 expression. The treated cells with whole bacteria presented a Bcl-2 expression of 40+/-6%, while Fas expression was not changed compared to controls. This study confirm that at the site of mycobacterial infection, necrosis, apoptosis or prolonged survival of the cells depend on the quantity and quality of the molecules expressed by the mycobacteria; whether necrosis or apoptosis or prolonged survival is more or less favorable to the host likely depends on several factors regarding the inflammatory and immune response, both markedly stimulated by mycobacteria.
Nuzzo
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Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Seconda Università degli Studi di Napoli, S. Aniello a Caponapoli, Italy.
Galdiero
M
M
Bentivoglio
C
C
Galdiero
R
R
Romano Carratelli
C
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003311:Cord Factors / Q000494:pharmacology*; D015870:Gene Expression; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000472:pathogenicity*; D009171:Mycolic Acids / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012307:Risk Factors; D013229:Stearic Acids / Q000494:pharmacology*; D019014:fas Receptor / Q000378:metabolism
D003311:Cord Factors; D009171:Mycolic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D013229:Stearic Acids; D019014:fas Receptor; C026082:tuberculostearic acid