Suppression of inducible nitric oxide synthase and cyclooxygenase-2 gene expression by 22(R)-hydroxycholesterol requires de novo protein synthesis in activated macrophages

Yasuda Toshimichi

Kanno Masamoto

Kawamoto Masashi

Yuge Osafumi

Ninomiya Yuichi

The Journal of Steroid Biochemistry and Molecular Biology

Liver X receptors (LXRs) play an important role in lipid metabolism. Recently, a role for these proteins was identified in suppressing the inflammatory response. However, it is not known whether the natural ligands of LXRs, e.g. 22(R)-hydroxycholesterol (22R-HC), can suppress the inflammatory response after the onset of inflammation. We demonstrate here that treatment of Lipopolysaccharide (LPS)-activated RAW264.7 macrophages with 22R-HC markedly suppressed nitric oxide (NO) production and inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression. Additionally, 22R-HC did not affect the DNA binding activity of NF-κB, AP-1 and C/EBP(s), important transcriptional factors for iNOS and COX-2 genes expression. Furthermore iNOS and COX-2 mRNA suppression by 22R-HC was diminished by cellular treatment with cycloheximide. These results suggest that 22R-HC suppresses the expression of iNOS and COX-2 genes through de novo protein synthesis of an unidentified protein in LPS-activated macrophages. © 2005 Elsevier Ltd. All rights reserved.

22(R)-Hydroxycholesterol

Inflammation

Macrophage

22R-HC

Medical sciences [ 490 ]

eng

Elsevier Ltd

Copyright (c) 2005 Elsevier Ltd

[ISSN] 0960-0760

[DOI] 10.1016/j.jsbmb.2005.06.030

[PMID] 16146692

[DOI] http://dx.doi.org/10.1016/j.jsbmb.2005.06.030 isVersionOf