Glucosamine suppresses interleukin-8 production and ICAM-1 expression by TNF-α-stimulated human colonic epithelial HT-29 cells

Abstract

Intestinal epithelial cells play an important role in the mucosal immune reaction in inflammatory bowel diseases via the production and expression of chemokines and adhesion molecules, such as interleukin-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1), which are involved in the neutrophil infiltration and tissue damage in the inflamed colon. Notably, glucosamine, a naturally-occurring amino monosaccharide, has been shown to exhibit an anti-inflammatory action by inhibiting neutrophil functions. In the present study, to evaluate the anti-inflammatory action of glucosamine on intestinal epithelial cells, we examined the effects of glucosamine on the activation of a human colonic epithelial cell line HT-29. The results revealed that glucosamine suppressed the IL-8 production and ICAM-1 expression by TNF-alpha-activated HT-29 cells. Furthermore, glucosamine inhibited the TNF-alpha-induced phosphorylation of p38MAPK and NF-kappaB p65, and the nuclear translocation of NF-kappaB in the cells. Thus, glucosamine demonstrates inhibitory actions on the inflammatory and signaling molecules (IL-8, ICAM-1, p38MAPK and NF-kappaB) in intestinal epithelial cells. However, glucosamine did not essentially affect the binding of TNF-alpha to its receptor on HT-29 cells. Together, these observations suggest that glucosamine may have the potential to exhibit an anti-inflammatory action on intestinal epithelial cells, by possibly interfering with the activation signaling downstream of the ligand/receptor binding.