Clonorchis sinensis excretory/secretory proteins ameliorate inflammation in rheumatoid arthritis and ankylosing spondylitis

中华肝吸虫的排泄/分泌蛋白可减轻类风湿性关节炎和强直性脊柱炎的炎症

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作者:Moon-Ju Kim # ,Hee Min Yoo # ,Yu Jeong Lee ,Hyun Hee Jang ,Seung Cheol Shim ,Eun Jeong Won ,Tae-Jong Kim

Background

We aimed to investigate whether substances secreted by Clonorchis sinensis excretory/secretory protein (CS-ESP) have an effect on the inflammation of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to identify specific peptides through related proteomic analysis to determine which proteins exhibit anti-inflammatory effects more specifically.

Conclusions

We provide evidence showing that CS-ESP, Cs-GT and Cs-Severin can ameliorate clinical signs and cytokine derangements in AS.

Methods

Peripheral blood mononuclear cells (PBMCs) were obtained from healthy controls (HCs), RA and AS patients. Cytotoxicity of CS-ESP at different doses was assessed by MTS and flow cytometry before performing experiments. Inflammatory cytokine producing cells were analyzed using flow cytometry. To determine the effect of CS-ESP in an arthritis mouse model, 8-week-old SKG mice were injected intraperitoneally with curdlan and treated with CS-ESP; body weight and paw swelling were checked twice a week. Inflammation was evaluated using immunohistochemistry. We conducted proteomic analysis on CS-ESP and identified specific Cs-GT and Cs-Severin proteins. In vitro effect of coculture with Cs-GT and Cs-Severin was determined by inflammatory cytokine measurements. Result: Treatment with CS-ESP resulted in no reduced cell viability of PBMCs. In experiments culturing PBMCs, the frequencies of IL-17A and GM-CSF producing cells were significantly reduced after CS-ESP treatment. In the SKG mouse model, CS-ESP treatment significantly suppressed clinical score, arthritis and enthesitis. Treatment with Cs-GT and Cs-Severin resulted in no reduced cell viability of HC PBMCs. After Cs-GT and Cs-Severin treatment of HC PBMC, the frequencies of IL-17A and GM-CSF producing cells were significantly reduced. Conclusions: We provide evidence showing that CS-ESP, Cs-GT and Cs-Severin can ameliorate clinical signs and cytokine derangements in AS.

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