SOCS3 suppresses the expression of IL-4 cytokine by inhibiting the phosphorylation of c-Jun through the ERK signaling pathway in rat mast cell line RBL-2H3.

SOCS3 is well known to negatively regulate various cytokine-mediated signaling responses, but its direct role in the expression of specific cytokines has not been clearly elucidated. To understand the role of SOCS3 in the expression of IL-4, one of the key Th2 cytokines, RBL-2H3 cells (a rat mast cell line) were engineered to express SOCS3 constitutively at a high level or at a lower level using shRNA. In RBL-2H3 cells stably expressing SOCS3, the RNA and protein levels of IL-4 were significantly decreased, while it was opposite in RBL-2H3 cells containing shRNA for SOCS3. Overexpression of SOCS3 was found to reduce the level of calcium ionophore-induced phosphorylation of ERK1/2 and c-Jun transcription factor. Consistent with this data, knockdown of SOCS3 increased the level of phosphorylated ERK1 and ERK2. Taken together, SOCS3 appears to play an important role as a negative feedback inhibitor in the expression of IL-4 by inhibiting serine phosphorylation of c-Jun via the ERK signaling pathway. Copyright Â