Bovine glycomacropeptide induces cytokine production in human monocytes through the stimulation of the MAPK and the NF‐κB signal transduction pathways

• Published in: British journal of pharmacology 2009-08, Vol.157 (7), p.1232-1240
• Main Authors: Requena, Pilar, Daddaoua, Abdelali, Guadix, Emilia, Zarzuelo, Antonio, Suárez, María Dolores, De Medina, Fermín Sánchez, Martínez‐Augustin, Olga
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; bovine glycomacropeptide; Medical sciences; NF‐κB; Pharmacology. Drug treatments; Research Papers; THP‐1 cells
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2009.00195.x

Background and purpose:  Bovine glycomacropeptide (BGMP) is a natural milk peptide that is produced naturally in the gastrointestinal tract during digestion. Glycomacropepide has intestinal anti‐inflammatory activity, but the mechanism of action is unknown. Here we have characterized the effects of BGMP on monocytes. Experimental approach:  We have used human THP‐1 cells as an in vitro monocyte model. The effect of BGMP on the secretion of tumour necrosis factor (TNF), interleukin (IL)‐1β and IL‐8 was assessed, as well as the involvement of the NF‐κB and MAP kinase signalling pathways. The stimulatory effect of BGMP was also tested in human peripheral blood monocytes. Key results:  BGMP up‐regulated the secretion of TNF, IL‐1β and IL‐8 in a concentration‐dependent fashion. The biological activity was exerted by the intact peptide, because cytokine secretion was not affected by protease inhibitors. The secretion of IL‐8 and specially TNF and IL‐1β was blocked by PD98059, SP600125, SB203580 and Bay11‐7082, suggesting the involvement of the MAP kinases p38, c‐Jun N‐terminal kinase and ERK and particularly the NF‐κB pathway, although IL‐8 secretion was independent of p38. BGMP was shown to elicit the phosphorylation of IκB‐α and the nuclear translocation of the NF‐κB subunits p50 and p65. The effect of BGMP on cytokine secretion was validated in human primary blood monocytes. Conclusions and implications:  BGMP stimulates human monocytes, operating via MAP kinase and NF‐κB pathways. BGMP may exert an indirect intestinal anti‐inflammatory effect by potentiating host defences against invading microorganisms.