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Anti-inflammatory roles of retinoic acid in rat brain astrocytes: Suppression of interferon-gamma-induced JAK/STAT phosphorylation.

Choi, WH; Ji, KA; Jeon, SB; Yang, MS; Kim, H; Min, KJ; Shong, M; Jou, I; Joe, EH
Biochemical and biophysical research communications, 329(1):125-131, 2005
Journal Title
Biochemical and biophysical research communications
The anti-inflammatory effect of retinoic acid (RA) has been investigated for several decades. However, the underlying mechanisms responsible for this effect are largely unknown. In this study, we demonstrate that 9-cis-RA (cRA) and all-trans-RA (tRA) inhibit interferon-gamma (IFN-gamma)-induced inflammatory responses in astrocytes. In primary cultured rat brain astrocytes and C6 astroglioma cells, both cRA and tRA decreased IFN-gamma-induced expression of interferon regulatory factor-1. Both RA isoforms also reduced IFN-gamma-induced activation of signal transducers and activators of transcription (STAT)1, STAT3, Janus kinase (JAK)1, and JAK2. This inhibitory effect was significant when cells were pre-treated with RA prior to IFN-gamma. Furthermore, the effect of pre-treated RA was abolished in the presence of cycloheximide, indicating a requirement for de novo protein synthesis. Suppressors of cytokine signaling (SOCS), which are negative regulators of the JAK/STAT pathway, may be candidate mediators of the anti-inflammatory function of RA. Both cRA and tRA induced SOCS3 mRNA expression. These results suggest that RA induces an anti-inflammatory effect by suppressing the activation of the JAK/STAT pathway in IFN-gamma-treated astrocytes. SOCS3 may be at least one of the mechanisms that mediate the anti-inflammatory roles of RA.
MeSH terms
AnimalsAnti-Inflammatory Agents/pharmacology*Astrocytes/metabolism*Blotting, WesternBrain/metabolism*Carrier Proteins/metabolismCycloheximide/pharmacologyDNA-Binding Proteins/metabolismInflammationInterferon-gamma/metabolism*Janus Kinase 1Janus Kinase 2Phosphorylation*Protein Synthesis Inhibitors/pharmacologyProtein-Tyrosine Kinases/metabolismProto-Oncogene Proteins/metabolismRNA, Messenger/metabolismRatsRats, Sprague-DawleyRepressor Proteins/metabolismReverse Transcriptase Polymerase Chain ReactionSTAT1 Transcription FactorSTAT3 Transcription FactorSuppressor of Cytokine Signaling ProteinsTrans-Activators/metabolismTranscription Factors/metabolismTretinoin/metabolism*Tretinoin/pharmacology*
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Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
양, 명순주, 일로조, 은혜
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