Up-regulation of tryptophan-2,3-dioxygenase 2 mediates the role of kynurenine metabolism in adjuvant arthritis in rats

Acta Universitatis Medicinalis Anhui 2022 09 v.57 1374-1379     font:big middle small

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Authors:Jia Chengyan; Han Ping; Wang Yueye; Xu Yuan; Xu Hepeng; Chen Ayuan; Wei Wei; Chang Yan

Keywords:rheumatoid arthritis;adjuvant arthritis;tryptophan-2,3-dioxygenase 2;kynurenine;tryptopha

DOI:10.19405/j.cnki.issn1000-1492.2022.09.006

〔Abstract〕 Objective To explore the changes of tryptophan-2,3-dioxygenase 2(TDO2) expression and its mediated kynurenine(Kyn) pathway in different inflammatory stages(initial period, peak period and remission period) of adjuvant arthritis in rats. Methods A rat model of AA was established.AA rats were sacrificed at different stages of inflammation.The pathological changes of joint synovium and liver were observed by HE staining; TDO2 expression in joint synovial tissue and liver tissue was detected by immunohistochemistry; High performance liquid chromatography was used to detect tryptophan(Trp) and Kyn levels in serum and liver. Results Compared with the normal group, AA rats showed similar clinical and pathological features to RA.The expression of TDO2 in rat joint synovium and liver tissue increased during the peak period and remission period(P<0.05).Trp levels in serum of AA rats at each inflammation stage decreased, and Kyn levels increased in the initial stage(P<0.01);Trp levels in the liver tissues of rats at the peak period decreased, Kyn levels increased, and Kyn/Trp ratio increased(P<0.01). Conclusion TDO2 may play an important role in the peak period of AA,and mediate Kyn metabolism to participate in the occurrence and development of RA.