Rapamycin Augments the NMDA-Mediated TNF Suppression of MRSA-Stimulated RAW264.7 Murine Macrophages
Figure 1
(a) Ketamine and the PI3 K/Akt inhibitor LY294002 modify TNF production by RAW264.7 murine macrophages. In the upper panel, compared to the not treated control-first column, MRSA-MW2 (USA400) stimulated less TNF secretion (18%) by macrophages when exposed to LY294002 (second column), more secretion (20%) when exposed to NMDA substrate (third column), and was not significantly different from the control TNF secretion (8% decrease) when both NMDA and LY294002 were present (fourth column). In the lower panel, ketamine (first column) was added and suppressed TNF production 35% less than the control (upper panel, first column). Ketamine and LY294002 (lower panel, second column) also caused TNF suppression (33%), but when compared with ketamine alone (lower panel, first column), the suppression was not significantly different. Ketamine and NMDA caused a 7% TNF increase (not different from the control at ), and ketamine-NMDA with LY294002 caused 17% TNF suppression. The results are depicted as fold of change compared to the control with 95% confidence intervals shown as “error bars.” . The control response was pg/mL. (b) AP5 (APV), another NMDA inhibitor, modified TNF production by RAW264.7 murine macrophages in a way similar to that of ketamine. In the upper panel MW2 (USA400) stimulated 15% less TNF secretion by macrophages when exposed to LY294002 (second column), 30% more when exposed to NMDA substrate (third column)—both significantly different from the untreated control (upper panel, first column) at . The TNF secretion in the presence of both NMDA and LY294002 (upper panel, fourth column) was not significantly different from the control. In the same experimental sequence in the lower panel, AP5 caused significant suppression of TNF production (25%—lower panel, first column) in a manner similar to that of ketamine (Figure 1, lower panel, first column). Of the rest, only the combination LY294002 and AP5 (second column) caused a significant suppression (33%) compared to control (). The results are depicted as fold of change compared to the control with 95% confidence intervals shown as “error bars.” . The control response was pg/mL.
