Enhancement of TNF-α Synthesis by Overexpression of G_αz in a Mast Cell Line

Ag stimulation of mast cells via the IgE receptor (Fc∈RI) elicits production and release of numerous cytokines. This activation of Fc∈RI initiates various tyrosine kinase-dependent signaling cascades, which ultimately result in the de novo synthesis of cytokines. To date, no heterotrimeric G proteins have been implicated in this process. Here we report that the a subunit of the heterotrimeric G protein, G_z, can regulate production of the cytokine, TNF-α. The α subunit was overexpressed in a cultured mast cell line (RBL-2H3) known to contain G_αz. In stimulated cells, overexpression of G_αz significantly enhanced the production of TNF-α. This effect of G_αz appeared to be restricted in that constitutive synthesis of the cytokine, TGF-β, and Ag-stimulation of the phosphoinositide-dependent secretory pathway were not significantly affected. Thus, G_az, a heterotrimeric G protein, appeared to modulate the stimulatory pathways for induction of TNF-α synthesis in RBL-2H3 cells.