Figure 4

Neuroprotective effect of telmisartan is partially mediated through inhibition of the c-Jun N-terminal kinase (JNK)/c-Jun pathway in SK-N-SH neuroblasts. (A) Telmisartan attenuated the time-dependent activation of JNK and c-Jun in response to interleukin-1 beta (IL-1β). The cells were pretreated for 2 hours with 10 μmol/l telmisartan (Telm) before exposure to 10 ng/ml IL-1β for the indicated time intervals. Phosphorylation of JNK and c-Jun was determined by western blotting. Representative blots are shown under the corresponding bar graphs. ### P < 0.001 vs. Veh; * P < 0.05, *** P < 0.001 vs. corresponding IL-1β group. (B) Telmisartan inhibited IL-1β-stimulated JNK and c-Jun activation with a potency similar to that of diphenyleneiodonium (DPI) but to a lesser extent than the JNK inhibitor SP600125. The cells were pretreated for 2 hours with 10 μmol/l Telm, 5 μmol/l DPI, or 10 μmol/l SP600125 (SP) before exposure for 30 minutes to 10 ng/ml IL-1β. The phosphorylation of JNK and c-Jun was detected as above. Results are shown as a percentage of the IL-1β-treated group. (C,D) The JNK inhibitor SP600125 abrogated the IL-1β-induced COX-2 mRNA expression and PGE₂ release. The cells were pretreated for (C) 2 hours with 10 μmol/l SP before exposure for 3 hours to 10 ng/ml IL-1β to determine COX-2 mRNA expression, or with (D) the indicated concentrations of SP600125 before exposure for 24 hours to 10 ng/ml IL-1β to determine cumulative PGE₂ release. All results are presented as means ± SEM from three independent experiments. *** P < 0.001 vs. IL-1β; ### P < 0.001 vs. Veh; $$$ P < 0.001 vs. IL-1β + Telm.