Vitamin A Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin A, including details on retinol, benefits, dosage, supplements, deficiency, information. | ||||||||
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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 Neuroscience Graduate Program, Ajou University School of Medicine, Suwon 442-721, Republic of Korea. 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. Published 21 February 2005 in Biochem Biophys Res Commun, 329(1): 125-31.
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