Destabilization of TNF-α mRNA by retinoic acid in hepatic macrophages: implications for alcoholic liver disease (original) (raw)

American Journal of Physiology-Endocrinology and Metabolism

Retinoic acid (RA) inhibits hepatic macrophage (HM) cytokine expression, and retinoids are depleted in alcoholic liver disease (ALD). However, neither the causal link between the two nor the mechanism underlying RA-mediated HM inhibition is known. The aim of the present study was to determine the mechanism of RA-induced inhibition of HM tumor necrosis factor (TNF)-α expression and the relevance of this regulation to ALD. Treatment with all- trans RA (500 nM) caused a 50% inhibition in lipopolysaccharide (LPS)-stimulated TNF-α expression by cultured normal rat HM. The mRNA levels for inducible nitric oxide synthase, interleukin (IL)-6, IL-1α, and IL-1β were also reduced, whereas those for transforming growth factor-β1, MMP-9, and membrane cofactor protein-1 were unaffected. The inhibitory effect on TNF-α expression was reproduced by LG268, a retinoid X receptor (RXR)-specific ligand, but not by TTNPB, an RA receptor (RAR)-specific ligand. RA did not alter LPS-stimulated NF-kB and act...

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