Browsing by Author "Sheu, Shiow-Yunn"

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Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1 beta-induced catabolic gene expression in cartilage
(2015-01-24)
Sheu, Shiow-Yunn
;
Ho, Shin-Rong
;
Sun, Jui-Sheng
;
Chen, Ching-Yun
;
Ke, Cherng-Jyh
Background: In osteoarthritis (OA), the imbalance of chondrocytes' anabolic and catabolic factors can induce cartilage destruction. Interleukin-1 beta (IL-1 beta) is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial cells to synthesize MMPs. The hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by Epas1) is the catabolic transcription factor in the osteoarthritic process. The purpose of this study is to validate the effects of ecdysteroids (Ecd) on IL-1 beta-induced cartilage catabolism and the possible role of Ecd in treatment or prevention of early OA. Methods: Chondrocytes and articular cartilage was harvested from newborn ICR mice. Ecd effect on chondrocytes viability was tested and the optimal concentration was determined by MTT assay. The effect of HIF-2 alpha (EPAS1) in cartilage catabolism simulated by IL-1 beta (5 ng/ml) was evaluated by articular cartilage explants culture. The effects of Ecd on IL-1 beta-induced inflammatory conditions and their related catabolic genes expression were analyzed. Results: Interleukin-1 beta (IL-1 beta) treatment on primary mouse articular cartilage explants enhanced their Epas1, matrix metalloproteinases (MMP-3, MMP-13) and ADAMTS-5 genes expression and down-regulated collagen type II (Col2a1) gene expression. With the pre-treatment of 10(-8)M Ecd, the catabolic effects of IL-1 beta on articular cartilage were scavenged. Conclusion: In conclusions, Ecd can reduce the IL-1 beta-induced inflammatory effect of the cartilage. Ecd may suppress IL-1 beta-induced cartilage catabolism via HIF-2a pathway.
Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity
(2015-09-14)
Sheu, Shiow-Yunn
;
Hong, Yi-Wen
;
Sun, Jui-Sheng
;
Liu, Man-Hai
;
Chen, Ching-Yun
Background: Hypoxia could lead to microglia activation and inflammatory mediators' overproduction. These inflammatory molecules could amplify the neuroinflammatory process and exacerbate neuronal injury. The aim of this study is to find out whether harpagoside could reduce hypoxia-induced microglia activation. Methods: In this study, primary microglia cells harvested from neonatal ICR mice were activated by exposure to hypoxia (1 % O-2 for 3 h). Harpagoside had been shown to be no cytotoxicity on microglia cells by MTT assay. The scavenger effect of harpagoside on hypoxia-enhanced microglial cells proliferation, associated inflammatory genes expression (COX-II, IL-1 beta and IL-6 genes) and NO synthesis were also examined. Results: Hypoxia enhances active proliferation of microglial cells, while harpagoside can scavenge this effect. We find that harpagoside could scavenge hypoxia-enhanced inflammatory genes expression (COX-2, IL-1 beta and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1 alpha (HIF-1 alpha) significantly increase, while the cytosol I kappa B-alpha content decreases; these effects can be reversed by 1 h's pre-incubation of 10(-8) M harpagoside. Harpagoside could decrease I kappa B-alpha protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-kappa B activation and reduce the HIF-1 alpha generation. Conclusion: These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-kappa B signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-alpha pathway.