Abstract

The mechanism underlying the wogonin-mediated increase in the expression of suppressor of cytokine signaling 3 (SOCS3) is unclear. Promoter deletion assay results revealed that wogonin-induced SOCS3 expression is dependent on the AP-1 consensus sequences and two STAT responsive elements (TTACAAGAA and TTCCAGGAA) in the 5′-flanking region of the SOCS3 gene in SH-SY5Y cells. Wogonin-induced SOCS3 expression was blocked by inhibitors of PI3K, Akt, Raf, p38, JNK, MEK, and STAT3, respectively. However, JAK2 inhibitors did not inhibit wogonin-induced SOCS3 expression. These results indicate that SOCS3-inducing effect of wogonin is caused by the activation of PI3K-mediated MAPK signaling pathways (Akt, ERK1/2, p38, and JNK), and the subsequent activation of AP-1 consensus sequences and STAT responsive elements in SH-SY5Y cells.

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