Figure 5

p38 MAPK activation mediates Tat-induced expression of proinflammatory cytokines, iNOS, SERT and IDO in OHSCs. (A) Tat induces Thr180/Tyr182 phosphorylation of p38 MAPK MAPK as early as 15 min with a maximum at 60 min in OHSCs. Hippocampal slices were treated with Tat (40 ng/slice) at 15, 30, 60 and 120 min, and cell lysates were collected for p38 MAPK phosphorylation analysis by Western blot. A representative Western blot showing results with hippocampal slices incubated with Tat at the above time points is shown, followed by densitometric analysis of Western blots from three independent experiments. Densitometric data were calculated as ratio of phosphorylated p38 MAPK to total p38 MAPK. Bars labeled with different letters (a, b or c) are significantly different from each other at p < 0.05. (B) The p38 MAPK inhibitor, SB 202190, abrogates Tat-induced expression of IDO, iNOS, SERT and proinflammatory cytokines. Hippocampal slices were treated with SB 202190 (30 μM) for 30 min and then incubated with or without Tat (40 ng/slice) for 6 h. SB 202190 inhibited Tat-induced IDO, iNOS, SERT, TNFα and IL-6 expression. Data represent the mean ± SEM (n = 3 in each group). ** p < 0.01 compared to medium control; ## p < 0.01 compared to Tat + SB treatment. SB = SB 202190.