[Liver X receptor alpha inhibits LPS-induced inflammation by down-regulating IFR3 and GRIP1 in mouse Kupffer cells].
OBJECTIVE
To explore the possible mechanism of the inhibitory effect of liver X receptor alpha (LXRalpha) on lipopolysaccharide (LPS)-induced inflammation in mouse Kupffer cells (KCs).


METHODS
The 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).


RESULTS
The 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).


CONCLUSIONS
Pre-treatment with T0901317 before LPS stimulation can suppress the expressions of IRF3 and GRIP1 to inhibit the inflammation and hence Kupffer cell activation.
Ou
Zhi-bing
ZB
Chongqing Key Laboratory of Hepatobliliary Surgery, Department of Hepatobliliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Huang
Qing-yong
QY
Sun
Ke
K
Wei
Si-dong
SD
Gong
Jian-ping
JP
Tu
Bing
B
D000818:Animals; D002478:Cells, Cultured; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced*; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D007728:Kupffer Cells / Q000166:cytology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D006845:Hydrocarbons, Fluorinated; D050838:Interferon Regulatory Factor-3; D008070:Lipopolysaccharides; D000071518:Liver X Receptors; D051958:Nuclear Receptor Coactivator 2; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C494233:Irf3 protein, mouse; C498002:Ncoa2 protein, mouse; C000605214:Nr1h3 protein, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides