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J Neurochem. 2010 Sep 1;114(5):1511-26. doi: 10.1111/j.1471-4159.2010.06867.x. Epub 2010 Jun 16.

Inflammatory chemokine release of astrocytes in vitro is reduced by all-trans retinoic acid.

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  • 1Institut für Biologie II, RWTH Aachen University, Germany.

Abstract

The production of chemokines by astrocytes constitutes an important component of neuroinflammatory processes in the brain. As the transcriptional activator retinoic acid (RA), used for chemotherapy and dermatological applications, exerts anti-inflammatory effects on monocytes and lymphocytes, we have tested whether the physiologically occurring isomer, all-trans RA, affects chemokine expression by astrocytes. Under control conditions, primary cultures of murine cortical astrocytes expressed no or very low levels of CCL and CXCL chemokines. After treatment with bacterial lipopolysaccharides to simulate inflammation in vitro, we detected a strong increase in the release of CCL2 (to > 4 ng/mL in cell culture supernatant), CCL3 (> 20 ng/mL), CCL5 (> 25 ng/mL), CXCL1 (> 30 ng/mL) and CXCL2 (> 20 ng/mL). Although simultaneous exposure to RA did not significantly affect this response, 12 h pre-treatment with 0.1 microM all-trans RA strongly suppressed mRNA expression and protein release of all chemokines. The anti-inflammatory activity of RA engaged RA and retinoid X receptors and correlated with a decreased expression of the lipopolysaccharides co-receptor CD14. A minor reduction of nuclear NF-kappaB was observed but not significant, activation of Jun amino-terminal kinase, p38 and signal transducer and activator of transcription 3 were not altered by RA. The results suggest that retinoids should be further investigated as candidates for the treatment of neuroinflammation.

PMID:
20557428
[PubMed - indexed for MEDLINE]
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