Anti-Inflammatory Properties of High Density Lipoprotein (HDL) on Intestinal Epithelial Cells

Abstract

G A A b st ra ct s and label-free detection. Results: Treatment of MM6 cells with TNF, but none of the other cytokines (IFN-γ, IL-1β, IL-6, TGF-β) tested, led to significant upregulation of GPR68 mRNA. Induction of GPR68 mRNA expression by TNF was dose-dependent. Macrophagic differentiation of MM6 cells with PMA also led to a significant increase in GPR68 mRNA expression. Dose-dependence of TNF and PMA induction of GPR68 mRNA was confirmed in primary human monocytes. In agreement with these findings, GPR activity in MM6 cells was increased upon treatment with TNF or PMA, only at acidic pH. In hypoxia, both 0.2% and 2% oxygen conditions synergized with TNF, PMA, and LPS in the induction of GPR68 mRNA expression. Furthermore, TNF-mediated induction of GPR68 mRNA expression was reversed by simultaneous treatment of cells with NF-κB inhibitors AICAR, BAY-11-7082, CAY10512, and SC-514. No induction of mRNA expression of the related GPRs, GPR4 and GPR65, was observed upon treatment with TNF, PMA, or LPS. Conclusion: GPR68 expression is induced in cells of human macrophage lineage and primary human monocytes by TNF, PMA, and LPS. NF-κB inhibition reverses the induction of GPR68 mRNA expression by TNF. Interestingly, hypoxia, also known to activate the NF-κB pathway, synergizes with TNF in the induction of GPR68 expression. TNF-mediated stimulation of GPR68 expression and subsequent pH-sensing activity may play a role in the molecular pathogenesis of IBD.