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  • Title: Association between liver X receptor-α and neuron-derived orphan nuclear receptor-1 in Kupffer cells of C57BL/6 mice during inflammation.
    Author: He K, Dai ZY, Li PZ, Zhu XW, Gong JP.
    Journal: Mol Med Rep; 2015 Oct; 12(4):6098-104. PubMed ID: 26239564.
    Abstract:
    The liver X receptor (LXR) isoform LXR‑α has a significant role in lipid metabolism and innate immunity. Overexpression of neuron‑derived orphan nuclear receptor‑1 (NOR‑1) in macrophages reduces the synthesis of inflammatory cytokines and chemokines. However, to date, the mechanisms via which NOR‑1 inhibits lipopolysaccharide (LPS)‑induced inflammation in Kupffer cells (KCs) via LXR‑α have not been elucidated. T0901317 is the most potent LXR‑α ligand, leading to its activation. In the present study, KCs were isolated from C57BL/6 mice and randomly divided into five groups: Control, T0901317, LPS, LPS + T0901317 and LPS + T0901317 + NOR‑1 small hairpin (sh)RNA groups. In order to investigate the role of NOR‑1 in inflammation, shRNA targeting NOR‑1 was used to specifically knock down NOR‑1 mRNA in KCs. The expression levels of LXR‑α and NOR‑1 in KCs were determined by reverse transcription quantitative polymerase chain reaction and western blot analyses. The protein levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑10 in the supernatant of KCs were evaluated by ELISA. The results revealed that LXR‑α expression in the T0901317 group was higher than that in the control group; furthermore, LXR‑α expression was higher in KCs treated with LPS + T0901317 compared with that in KCs treated with LPS only. The expression levels of NOR‑1 in each group showed a similar trend. shRNA targeting of NOR‑1 suppressed the mRNA expression of NOR‑1, but had no influence on LXR‑α mRNA expression. NOR‑1 protein expression was augmented in the LPS + T0901317 group compared with that in the LPS + T09 + shRNA group. In the supernatant of KCs, the TNF‑α levels in the LPS + T0901317 group were lower than those in the LPS group, whereas the IL‑10 levels were higher in the LPS + T0901317 group compared with those in the LPS group. The results of the present study suggested that ligand T0901317 promotes LXR‑α expression, which consequently suppresses LPS‑induced inflammation by elevating NOR‑1 expression in KCs.
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