12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) induces cell growth and improves barrier function through BLT2 interaction in intestinal epithelial Caco-2 cell cultures

Abstract

12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is an unusual product of the cyclooxygenase pathway that is an endogenous ligand of the low-affinity receptor for leukotriene 4 (LTB₄), BLT2. Recent findings suggested that BLT2 possibly plays an important role in the healing of intestinal lesions and the regulation of barrier function. Here, we studied the role of 12-HHT on intestinal epithelial cell growth and the paracellular permeability of intestinal epithelium using Caco-2 cell cultures as experimental model. Our results demonstrated that 12-HHT stimulates intestinal epithelial Caco-2 cell growth through 12-HHT-BLT2-p38-PKC axis and improves paracellular permeability in differentiated Caco-2 cell cultures through the regulation of tight junction elements such as myosin light chain phosphorylation through 12-HHT-BLT2-p38-PKC-MYPT1 axis. Thus, 12-HHT-BLT2 interaction can be involved in intestinal epithelial cell growth and consequently in the epithelium regeneration/repair processes, together with an interesting improvement on the paracellular permeability. These effects appoint that 12-HHT/BLT2 axis may be a suitable strategy for treating wound healing epithelium and barrier-disrupted intestinal processes.

Keywords: Cell signalling; Colorectal cancer; Eicosanoid; Intestinal inflammation.