羥氯奎及其衍生物增強降植烷誘導的狼瘡小鼠的胞吞作用並調節腸道微生物組

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B857
Abstract ID: 4594

Presenting Author:
Gregory J Tsay , Professor at China Medical University Hospital

Abstract:

Background Impaired clearance of apoptotic cells (efferocytosis) and microbiota dysbiosis is related to pathogenesis of systemic lupus erythematosus (SLE). Hydroxychloroquine (HCQ) is frequently prescribed for the treatment of SLE. Here, we evaluate changes in efferocytosis and the gut microbiome in mice with pristane-induced lupus (PIL) by HCQ administration.

 

Methods PIL mice were studied with or without HCQ, the HCQ derivatives were modified from HCQ by molecular modification. Efferocytosis was determined in RAW 264.7 cells and peritoneal macrophages from mouse ascites fluid. The gut microbiome was analyzed using Illumina sequencing.

 

Results HCQ enhanced efferocytosis in RAW 264.7 cells, the HCQ derivative AL127 also much enhanced efferocytosis. HCQ also significantly suppressed ascites production of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in PIL mice. The Firmicutes/Bacteroidetes (F/B) ratio was notably decreased in comparison to untreated controls (p<0.05). Furthermore, administration of HCQ in PIL mice resulted in an increased F/B ratio.

 

Conclusions In this study, both HCQ and its derivative exhibited a capacity to enhance efferocytosis in RAW 264.7 cells and peritoneal macrophages of PIL mice. Furthermore, HCQ treatment reversed the pristane-induced reduction in the Firmicutes/Bacteroidetes (F/B) ratio. These findings underscore the roles of HCQ in facilitating efferocytosis.