Figure 2. IL-6 upregulation by MeHg is mediated by P2Y1 receptors followed by p38 activation.
(A) P2Y1 receptor blockade suppresses IL-6 mRNA expression induced by MeHg. MeHg (3 µM, 2 hr)-increased IL-6 mRNA expression was inhibited by either suramin (sur, 100 µM) or MRS2179 (MRS, 10 µM). *P<0.05 vs. MeHg. (B) P2Y1 receptor mediates MeHg-induced IL-6 mRNA expression. P2Y1R KO astrocytes exhibited no increase in IL-6 mRNA with MeHg (3 µM, 2 hr). **P<0.01 vs. WT. (C) Contribution of p38 in MeHg-induced IL-6 mRNA expression. The IL-6 mRNA expression evoked by MeHg (3 µM, 2 hr) was inhibited by SB203580 (SB, 10 µM) but not by PD98059 (PD, 10 µM) or SP600125 (SP, 10 µM). *P<0.05 vs. MeHg. (D) Downstream signaling molecule of P2Y1 receptor is p38. MeHg (3 µM, 30 min)-induced p38 phosphorylation was inhibited by suramin (sur, 100 µM). ATP (100 µM) also induced p38 phosphorylation. *P<0.05, **P<0.01 vs. control, #P<0.05 vs. MeHg.