Inhibition of Adenylyl Cyclase by α Chemokines IL-8 and GRO-α in Chinese Hamster Ovary Cells Expressing R1 and R2 Receptors

Abstract

Interleukin-8 (IL-8) and growth-related oncogene protein-α (GRO-α) belong to a family of α chemokines. The biologic effects of IL-8 are realized by binding to two seven-transmembrane receptors R1 and R2 and that of GRO-α by binding to receptor R2. Chinese hamster ovary (CHO) cells stably expressing R1 and R2 have been used to demonstrate that the ligand-dependent signaling by both receptors is via the inhibition of adenylyl cyclase. This inhibition is pertussis toxin sensitive and could be mediated by Gαi2, which is present in CHO cells. GRO-α inhibits adenylyl cyclase exclusively in CHO-R2 cells, and IL-8 inhibits in both CHOR1 and CHO-R2 cells. The cAMP status in cells is an easy, reliable, quantifiable signal that is amenable to high throughput screening for small molecule analogs.