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Retinoic acid inhibits expression of TNF‐α and iNOS in activated rat microglia
Author(s) -
Dheen S. Thameem,
Jun Yan,
Yan Zhou,
Tay Samuel S.W.,
Ang Ling Eng
Publication year - 2005
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20153
Subject(s) - microglia , neurotoxicity , nitric oxide synthase , tumor necrosis factor alpha , proinflammatory cytokine , retinoic acid , biology , nitric oxide , lipopolysaccharide , neurodegeneration , inflammation , immunology , endocrinology , pharmacology , medicine , biochemistry , toxicity , gene , disease
The release of proinflammatory mediators such as tumor necrosis factor‐α (TNF‐α) 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‐α and inducible nitric oxide synthase (iNOS) in microglia activated by β‐amyloid peptide (Aβ) and lipopolysaccharide (LPS). Exposure of primary cultures of rat microglial cells to Aβ or LPS stimulated the mRNA expression level of TNF‐α (6–116‐fold) and iNOS (8–500‐fold) significantly. RA acted in a dose‐dependent manner (0.1–10 μM) by attenuating both TNF‐α (29–97%) and iNOS (61–96%) mRNA expression in microglia exposed to Aβ or LPS. RA‐induced inhibition of TNF‐α and iNOS mRNA expression in activated microglia was accompanied by the concomitant reduction in release of iNOS and TNF‐α 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‐β, and transforming growth factor‐β1 as well as the inhibition of NF‐κB translocation. These results suggest that RA may inhibit the neurotoxic effect of activated microglia by suppressing the production of inflammatory cytokines and cytotoxic molecules. © 2004 Wiley‐Liss, Inc.