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Aim To observe the therapeutie effeet of (AA) rats and its effect on the aetivity of tryptophan allopurinol ( ALLO) on adjuvant induced arthritis 2,3 dioxygenase (TDO).Methods SD rats were randomly divided into normal group, AA model group, ALLO group (10,20 , 40 mg • kg 1 ) and methotrexate group (0.5 mg • kg 1 ).The AA rats were established by intracutaneous injection of complete Freund's adju¬vant into the right toes of rats.The body weight,joint swelling number, joint pathology, spleen index and fi¬broblast like synoviocytes ( FLS) proliferation of the rats were observed to explore the therapeutic effect of ALLO.Flow cytometry detected the number of CD68 ∗ macrophages and the ratio of Thl7/Treg of spleen.The concentration of tryptophan ( Trp) and kvnurenine ( Kyn) in the liver and the supernatant of FLS were de¬termined by high performance liquid chromatography.Results Compared with model group, ALLO adminis¬ tration significantly increased the body weight of AA rats, reduced the number of joint swelling, improved joint pathological injury,decreased spleen index,inhib¬ited the proliferation of FLS, reduced the number of macrophages in the spleen,decreased Thl7/Treg ratio, inhibited the metabolism of Tip and the production of Kyn in liver and FLS culture supernatant, and de¬creased the liver Kyn/Trp ratio (TOO activity).Con¬clusion ALLO has therapeutic effect on AA rats, which may be related to its regulation of TDO-mediated kyn metabolism pathway.
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Metabolomics studies have shown metabolic disorders in patients with rheumatoid arthritis (R A) . However, the metabolic characteristics of individual cell types associated with RA have sparsely been elucidated. Fibroblast-like synoviocytes (FLS) are the main cell types at the synovial tissue of joint, which can lead to joint destruction through invading articular cartilage. In the microenvironment of inflammatory tissues, the metabolism of glucose, lipids, amino acids, glutamine and other key nutrients in RA-FLS changes, which are involved in the abnormal activation of FLS and disease activities. The research progress on key molecules of RA-FLS energy metabolism abnormalityin recent years were summarized in this paper, providing a basis for elucidating the pathological mechanism of RA and discovering new drug targets.
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OBJECTIVE Aryl hydrocarbon receptor (Ahr) is thought to be a crucial factor that regulates immune responses, which may be involved in the pathogenesis of autoimmune inflammation including rheumatoid arthritis (RA). The results of our group in recent years have shown that CP-25, a novel ester derivative of paeoniflorin, has a good effect on improving RA animal models. However, whether the anti-arthritis effect of CP-25 is related to Ahr remains unclear. METHODS CP-25 treatment ameliorated adjuvant-induced arthritis (AA), a mouse model of RA, by inhibiting Ahr-related activities in fibroblasts like synoviocytes (FLS). AA rats were treated with CP-25 or paroxetine from day 17 to 33 after immunization. RESULTS CP-25 alleviated arthritis symptoms and the pathological changes, decreased the expression of Ahr in the synovium and FLS of AA rats. Besides, treatment with CP-25 reduced the proliferation and migration of MH7A caused by Ahr activation. In addition, we also demonstrated that CP-25 down-regulated the co-expres?sion and co-localization of Ahr and G protein-coupled receptor kinase 2 (GRK2) in MH7A. CONCLUSION The data pre?sented here demonstrated that CP-25 suppressed FLS dysfunction in rats with AA, which were associated with reduced Ahr activation and the interaction between Ahr and GRK2.