Activation of liver X receptors inhibit LPS-induced inflammatory response in primary bovine mammary epithelial cells

摘要

Liver X Receptors (LXRs) belong to the nuclear receptor superfamily, have been reported that activation of LXRs with synthetic ligands has anti-inflammatory effects in various inflammatory diseases. This study aims at investigating the effects of T0901317 (T0), a synthetic LXRs ligand, on lipopolysaccharide (LPS)-stimulated primary bovine mammary epithelial cells (bMECs). BMECs were stimulated by LPS in the presence or absence of T0. The results showed that treatment with T0 significantly inhibited LPS-induced tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) expression. LPS-induced NF-kappa B activation was also suppressed by TO. Furthermore, TO was found to inhibit the translocation of TLR4 to lipid rafts. TO could activate ATP-binding cassette transporter A1 (ABCA1) dependent pathway which induced cholesterol efflux from cells and disrupted the formation of lipid rafts. Thus, based on those findings we proposed that LXRs agonist might become a novel therapeutic target for inflammation.