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

• Published in: International immunopharmacology 2011-11, Vol.11 (11), p.1685-1690
• Main Authors: Zhang, Jing-Ge, Cong, Bin, Jia, Xian-Xian, Li, Hui, Li, Qiao-Xia, Ma, Chun-Ling, Feng, Yu
• Format: Article
• Language: English
• Subjects: Animals; B cells; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Cholecystokinin; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Immunoglobulin; Immunoglobulin G - biosynthesis; Immunoglobulin G - genetics; Lipopolysaccharide; Lipopolysaccharides - pharmacology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Pharmacology. Drug treatments; Receptors, Cholecystokinin - antagonists & inhibitors; Receptors, Cholecystokinin - physiology; Sincalide - pharmacology; Sincalide - physiology; Transcription, Genetic - drug effects
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2011.05.027

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. ► CCK-8 inhibits IgG1 expression and production in LPS-activated B cells. ► CCK-8 inhibits LPS-activated B cell proliferation and differentiation. ► CCK-8 regulates transcription factors Blimp1, Pax5, Xbp1 and Bcl6. ► The inhibitory action of CCK-8 is mainly mediated by the CCK2R pathway.