Cholecystokinin octapeptide inhibits immunoglobulin G1 production of lipopolysaccharide-activated B cells.

Cholecystokinin octapeptide (CCK-8) is a typical brain-gut peptide that exerts a variety of physiological actions in both the peripheral and central nervous systems. Our laboratory has previously reported that CCK-8 produces immunoregulatory action through activating CCK receptor (CCK1R/CCK2R) expression on immune cell surfaces. In the present study, we investigated the effect of CCK-8 on immunoglobulin G1 (IgG1) production in lipopolysaccharide (LPS)-activated B cells in vitro. CCK-8 inhibited the proliferation and IgG1 mRNA expression of LPS-activated B cells and therefore inhibited IgG1 production. The mechanism may be associated with the regulation of CCK-8 on transcription factors Blimp1, Pax5, Xbp1 and Bcl6. CCK-8 inhibited the expression of Blimp1, while the effect on Pax5, Xbp1 and Bcl6 varied with time, suggesting that CCK-8 acted as a complex regulator of LPS-activated B cells. The inhibitory action of CCK-8 was mainly mediated through the CCK2R pathway. These studies indicate that CCK-8 attenuates humoral immune responses and acts as endogenous immune deactivators in autoimmune diseases.