The specific mechanism of PGE2 inhibiting TDO2 expression and activity regulation of macrophage function changes
10.19405/j.cnki.issn1000-1492.2024.07.001
- Author:
Yi Wang
1
;
Siyu Li
1
;
Yueye Wang
1
;
Weibo Dong
1
;
Meng Cheng
1
;
Wei Wei
1
;
Yan Chang
1
Author Information
1. Institute of Clinical Pharmacology，Key Laboratory of Anti-inflammatory and Immunological Drugs of the Ministry of Education，Anhui Collaborative Innovation Centre for Anti-inflammatory and Immunological Drugs，Rheumatoid Arthritis Research Centre of Anhui Medical University，Hefei 230032
- Publication Type:Journal Article
- Keywords:
rheumatoid arthritis;
collagen-induced arthritis;
tryptophan-2，3-dioxygenase;
prostaglandin E2;
prostaglandin receptor 4
- From:
Acta Universitatis Medicinalis Anhui
2024;59(7):1107-1115
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the effects of tryptophan-2，3-dioxygenase ( TDO2 ) on collagen-induced ar- thritis，the expression of CIA in mice and the specific mechanism by which prostaglandin E2 (PGE2) inhibits the expression and activity of TDO2 and thus regulates the function of macrophages．
Methods :Type Ⅱ collagen in- duced the CIA model in DBA /1J mice．The ankle joint injury of CIA mice was detected by X-ray．The expression of TDO2 in ankle joint and spleen was detected by immunohistochemistry．Changes of TDO2 expression in perito- neal macrophages (PMs) were detected by qPCR and immunofluorescence．TDO2 expression was detected by small interference in RAW264. 7 cells，TDO2 inhibitor 680C91，PGE2 stimulation with different concentrations (0. 1，1， 10 μmol / L) and EP4 receptor agonist CAY10598．qPCR and Western blot were used to detect TDO2 expression. The phagocytosis and polarization of macrophages were detected by flow cytometry．The activity of TDO2 was detec- ted by colorimetry.
Results :Compared with normal mice，CIA mice had larger soft tissue swelling in ankle，and increased TDO2 expression in synovium，spleen and PMs．In RAW264. 7 cells，TDO2 expression was significantly inhibited after small interference ， TDO2 inhibitor 680C91 ， PGE2 stimulation ， and EP4 receptor agonist CAY10598，macrophage phagocytosis decreased ，and M1 / M2 ratio decreased ( P ＜0. 05 ) ． Colorimetric results showed that the activity of TDO2 was inhibited after stimulation of PGE2 and EP4 agonist CAY10598 in RAW264. 7 cells (P＜0. 05) ．
Conclusion :The increased expression of TDO2 in macrophages may promote synovial injury in CIA mice，and PGE2 regulates the function of macrophages by inhibiting the expression and activity of TDO2 by ac- tivating EP4 receptor.
- Full text:2024091015593686625PGE2抑制TDO2表达和...调控巨噬细胞功能变化的机制_王燚.pdf
