Retinoic acid inhibits expression of TNF-α and iNOS in activated rat microglia

被引:182
作者
Dheen, ST [1 ]
Jun, Y [1 ]
Yan, Z [1 ]
Ling, EA [1 ]
机构
[1] Natl Univ Singapore, Dept Anat, Mol Neurobiol Lab, Fac Med, Singapore 117597, Singapore
关键词
microglia; retinoic acid; TNF-alpha; TGF beta; iNOS; RAR beta; NF-kappa B;
D O I
10.1002/glia.20153
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The release of proinflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) and nitric oxide by microglia has been implicated in neurotoxicity in chronic neurodegenerative diseases such as Alzheimer's disease. As all-trans-retinoic acid (RA) has been reported to exert anti-inflammatory actions in various cell types, we have examined its effects on the expression of TNF-alpha and inducible nitric oxide synthase (iNOS) in microglia activated by beta-amyloid peptide (Abeta) and lipopolysaccharide (LPS). Exposure of primary cultures of rat microglial cells to Abeta or LPS stimulated the mRNA expression level of TNF-alpha (6-116-fold) and NOS (8-500-fold) significantly. RA acted in a dose-dependent manner (0.1-10 muM) by attenuating both TNF-alpha (29-97%) and iNOS (61-96%) mRNA expression in microglia exposed to Abeta or LPS. RA-induced inhibition of TNF-a and iNOS mRNA expression in activated microglia was accompanied by the concomitant reduction in release of iNOS and TNF-alpha proteins as revealed by nitrite assay and ELISA, respectively. The anti-inflammatory effects of RA were correlated with the enhanced expression of retinoic acid receptor-beta, and transforming growth factor-beta1 as well as the inhibition of NF-kappaB translocation. These results suggest that RA may inhibit the neurotoxic effect of activated microglia by suppressing the production of inflammatory cytokines and cytotoxic molecules. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:21 / 31
页数:11
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