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Murine non-parenchymal liver cells (NPC) and hepatocyte cultures were isolated, stimulated with TLR 1-9 ligands, and treated with dexamethasone. Changes in TLR 1-9 expression were measured quantitatively through quantitative reverse transcription PCR. Effects on TLR signaling were measured through TNF alpha, IL- 1b, IL-6, and IL-10 expression levels.
For LSECs, KCs, and hepatocytes treated with dexamethasone, TLR 9 expression (among others) were suppressed. The effect on KCs was especially significant where the pre-treatment with dexamethasone significantly suppressed TNF alpha expression by 50-80 and TLR induced IL-6 expression was completely suppressed to its basal levels. Dexamethasone also induced a strong suppression of IL-1b expression. The effect on LSECs is seen when the pre-treatment with dexamethasone resulted in a 30-80 suppression of TNF alpha expression and a 30-90 suppression of TLR induced IL-6 expression. In hepatocytes, pre-treatment with dexamethasone suppressed IL-1b expression by 80-100, however IL-10 expression was not affected. In addition, through examining the western blot analysis, it was found that pre-treatment with dexamethasone had selective effects on TLR-induced NF-kB activation. Specifically the TLR 1,2,3,4,7, and 9 induced NF-kB activation was inhibited by 60-85 (P0.05).
Dexamethasone is a potent immunomodulator and works by altering the inflammatory response of the innate immune system. It has varying effects on the TLR system that switches the body from an inflammatory state to an anti-inflammatory state.
Broering R. Corticosteroids shift the toll-like receptor response pattern of primary-isolated murine liver cells from an inflammatory to an anti-inflammatory state. International Immunology. 2011; 9: 537-44.