OBJECTIVETo explore the possible mechanism of the inhibitory effect of liver X receptor alpha (LXRalpha) on lipopolysaccharide (LPS)-induced inflammation in mouse Kupffer cells (KCs).

METHODSThe KCs isolated from the liver of male KM mice and cultured in RPMI 1640 containing 20% FBS for 24 h were divided into control, LPS, T0901317, and LPS+T0901317 groups with corresponding treatments. The expressions of LXRalpha, interferon regulatory factor 3 (IRF3) and glucocorticoid receptor interacting protein 1 (GRIP1) in the KCs were detected by Western blotting. The levels of interferon beta (IFNbeta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTSThe level of LXRalpha protein was highest in T0901317 group and lowest in LPS group, and was significantly higher in LPS+T0901317 group than in LPS group but lower than in T0901317 group (P<0.05). The levels of IRF3 and GRIP1 protein were the highest in LPS group, and significantly lowered by T0901317 treatment (P<0.05). The expression of IRF3 and GRIP1 proteins in LPS group and LPS+ T0901317 group were significantly higher than those in the control and T0901317 groups (P<0.05). The concentration of IFN-beta was significantly higher in LPS group than in the control and T0901317 group (P<0.05), and decreased in LPS+T0901317 group in comparison with that in LPS group (P<0.05). IFN-beta was the lowest in T0901317 group. The levels of TNF-alpha and IL-1beta were the highest in LPS group (P<0.05), and comparable between the other 3 groups (P>0.05).

CONCLUSIONPre-treatment with T0901317 before LPS stimulation can suppress the expressions of IRF3 and GRIP1 to inhibit the inflammation and hence Kupffer cell activation.

Animals ; Cells, Cultured ; Hydrocarbons, Fluorinated ; pharmacology ; Inflammation ; chemically induced ; Interferon Regulatory Factor-3 ; metabolism ; Kupffer Cells ; cytology ; metabolism ; Lipopolysaccharides ; pharmacology ; Liver X Receptors ; Male ; Mice ; Nuclear Receptor Coactivator 2 ; metabolism ; Orphan Nuclear Receptors ; physiology ; Sulfonamides ; pharmacology