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

Abstract

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. 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)-1beta and IL-8 was assessed, as well as the involvement of the NF-kappaB and MAP kinase signalling pathways. The stimulatory effect of BGMP was also tested in human peripheral blood monocytes. BGMP up-regulated the secretion of TNF, IL-1beta 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-1beta 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-kappaB pathway, although IL-8 secretion was independent of p38. BGMP was shown to elicit the phosphorylation of IkappaB-alpha and the nuclear translocation of the NF-kappaB subunits p50 and p65. The effect of BGMP on cytokine secretion was validated in human primary blood monocytes. BGMP stimulates human monocytes, operating via MAP kinase and NF-kappaB pathways. BGMP may exert an indirect intestinal anti-inflammatory effect by potentiating host defences against invading microorganisms.