Go is required for the release of IL-8 and TNF-α, but not degranulation in human mast cells.

Mast cells activated by IgE-dependent and -independent mechanisms play important roles in innate and acquired immune responses. Activation of pertussis toxin (PTX)-sensitive Gi/o proteins is the key step in mast cell degranulation and release of de novo synthesized inflammatory mediators through IgE-independent mechanism. However, the roles of Gi and Go proteins in mast cells activation have not yet been differentiated. In the current study, the functional roles of Go proteins in the activities of LAD2 cells, a human mast cell line, are identified. Knockdown of Gαo expression significantly inhibited the synthesis of IL-8 and TNF-α from substance P activated LAD2 cells but demonstrated no effect on degranulation. This effect was associated with the activation of Erk and JNK/MAPKs signaling, whereas PI3K-Akt, calcium mobilization and NFAT translocation remained unchanged. These results suggest that Gi and Go proteins differentially regulate human mast cells activities through activating distinct signaling cascades.