Abstract:

Objective To investigate the influence and underlying mechanism of Mycobacterium tuberculosis infection on aerobic glycolysis in macrophage. Methods U937 cells were infected with Mycobacterium tuberculosis H37Rv. At 0,30,60 and 90 min after infection,lactate production was determined. The routinely cultured U937 cells were classified into infection group（infected with Mycobacterium tuberculosis H37Rv for 60 min）,infection+SB203580 group [p38 mitogen-activated protein kinase（MAPK） inhibitor],infection+small interfering RNA（siRNA）-scramble group,infection+siRNA-6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3（PFKFB3） group and control group. Real-time quantitation polymerase chain reaction（qRT-PCR） and western blotting were used to determine PFKFB3. The expression of phosphorylated p38 MAPK（p-p38 MAPK） and the production of tumor necrosis factor（TNF）-α,interleukin（IL）-1β,IL-6 and lactate were determined in different groups. Results The expression of PFKFB3 and the production of lactate were increased in U937 cells induced by Mycobacterium tuberculosis H37Rv,both reaching the peak at 60 min. SB203580 could effectively inhibit the expressions of p-p38 MAPK and PFKFB3. However,silencing PFKFB3 expression abated the enhancement of inflammatory cytokine and aerobic glycolysis induced by Mycobacterium tuberculosis. Conclusions Infection with Mycobacterium tuberculosis up-regulates PFKFB3 expression and promotes aerobic glycolysis and inflammatory cytokine secretion via activating p38 MAPK signaling pathway.

Key words: Mycobacterium tuberculosis, Infection, Macrophage, Aerobic glycolysis