RGD Reference Report - Retinoic acid inhibits expression of TNF-alpha and iNOS in activated rat microglia. - Rat Genome Database
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Retinoic acid inhibits expression of TNF-alpha and iNOS in activated rat microglia.

Authors: Dheen, ST  Jun, Y  Yan, Z  Tay, SS  Ling, EA 
Citation: Dheen ST, etal., Glia. 2005 Apr 1;50(1):21-31.
RGD ID: 1582142
Pubmed: (View Article at PubMed) PMID:15602748
DOI: Full-text: DOI:10.1002/glia.20153

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 iNOS (8-500-fold) significantly. RA acted in a dose-dependent manner (0.1-10 microM) 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-alpha 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.


Gene Ontology Annotations    

Biological Process

Cellular Component
cytoplasm  (IDA)

Objects Annotated

Genes (Rattus norvegicus)
Nos2  (nitric oxide synthase 2)
Tnf  (tumor necrosis factor)

Additional Information