Vitamin D3 derivatives increase soluble CD14 release through ERK1/2 activation and decrease IL-8 production in intestinal epithelial cells

Dysfunction of he innate immune system has been reported to cause intestinal inflammation. Vitamin D3 is known to be an important immune system regulator and exerts anti-inflammatory effects. We investigated in vitro effects of vitamin D3 and its derivatives on the innate immune system in HT-29 cells, a line of human colon adenocarcinoma cells. Among the innate immune-related receptors such as Toll-like receptor (TLR) 1, 2, 4, 6, and CD14 examined by flow cytometry, only CD14 was up-regulated by vitamin D-3 derivatives. Release of soluble form CD14 (5CD14) was also increased by vitamin D-3 derivatives. The 1a,25-dihydroxy-22-oxavitamin D3 (Oxa-D-3) induced-5CD14 release was inhibited by 1J0126 (a specific inhibitor of extracellular signal-regulated kinase; ERK1 /2) but not by SB203580 (a specific inhibitor of p38 MAPK), and ERK1 /2 phosphorylation was accelerated by Oxa-D-3. These results indicate that Oxa-D3 facilitates the release of sCD14 through ERK1/2 activation. fL-8 production stimulated with [PS was diminishecl by vitamin D3 derivatives. Recombinant 5CD14 also lowered the [PS-stimulated IL-8 production, suggesting neutralization of [PS by 5CD14. The anti-inflammatory effect of vitamin D3 derivatives was thus associated with diminution of fL-8 production due to increased release of sCD14. (C) 2013 Elsevier B.V. All rights reserved.