[Liver X receptor alpha inhibits LPS-induced inflammation by down-regulating IFR3 and GRIP1 in mouse Kupffer cells].

Abstract

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).

CONCLUSION:

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

• Authors: Zhi-bing Ou, Qing-yong Huang, Ke Sun, Si-dong Wei, Jian-ping Gong, Bing Tu
• Journal: Nan fang yi ke da xue xue bao = Journal of Southern Medical University (Nan Fang Yi Ke Da Xue Xue Bao) Vol. 29 Issue 5 Pg. 848-51 (May 2009) ISSN: 1673-4254 [Print] China
• PMID: 19460690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydrocarbons, Fluorinated
• Interferon Regulatory Factor-3
• Irf3 protein, mouse
• Lipopolysaccharides
• Liver X Receptors
• Ncoa2 protein, mouse
• Nr1h3 protein, mouse
• Nuclear Receptor Coactivator 2
• Orphan Nuclear Receptors
• Sulfonamides
• T0901317

Topics

• 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)