ABSTRACT
Rheumatoid arthritis (RA) is an autoimmune disease characterized by excessive activation of autoreactive T cells and B cells, abundant production of autoantibodies and multiple joint involvement. Under the influence of heredity and environment, the disorder of innate immunity and adaptive immunity is the fundamental cause of the disease. In recent years, with rapid development of immunometabolism, milestone has been made in regulating the differentiation and function of immune cells through different energy metabolism pathways and related molecules. Many studies have shown that Trp-IDO1,2/TDO2-Kyn metabolic pathway mediates the pathogenesis and development of autoimmune diseases such as RA. This review summarizes the role of tryptophan (Trp), kynurenine (Kyn) and other metabolites in this metabolic pathway, as well as the role of rate-limiting enzymes indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2) and tryptophan-2,3-dioxygenase 2 (TDO2) in mediating RA inflammatory immune response and synovitis inflammation. This provides an important basis for elucidating the new pathological mechanism of RA and discovering new drug targets.
ABSTRACT
AIM:To investigate the effects of indoleamine 2,3-dioxygenase 2 (IDO2) silencing on proliferation,migration and invasion of B16-BL6 melanoma cells.METHODS:IDO2-siRNA was transfected into the B16-BL6 melanoma cells in vitro.The expression of IDO2 or IDOl at mRNA and protein levels was detected by real-time PCR and Western blot.Colony formation assay was performed to analyze the proliferation of IDO2-silencing tumor cells.The migration ability of B16-BL6 cells after silencing of IDO2 was measured by wound healing assay and Transwell cell migration assay.The invasion ability of the tumor cells was detected by Transwell cell invasion assay.RESULTS:IDO2-siRNA significantly down-regulated IDO2 expression in B16-BL6 melanoma cells,and did not affect IDO1 expression.Compared with control group,the colony formation ability,the migratory distance measured by wound healing assay,and the migration and the invasion cell numbers detected by Transwell assay all remarkably decreased in the IDO2-silencing cells.CONCLUSION:IDO2 silencing affects the proliferation,migration and invasion abilities of the R16-BL6 melanoma cells.
ABSTRACT
AIM:To investigate the effects of indoleamine 2,3-dioxygenase 2 (IDO2) silencing on proliferation,migration and invasion of B16-BL6 melanoma cells.METHODS:IDO2-siRNA was transfected into the B16-BL6 melanoma cells in vitro.The expression of IDO2 or IDOl at mRNA and protein levels was detected by real-time PCR and Western blot.Colony formation assay was performed to analyze the proliferation of IDO2-silencing tumor cells.The migration ability of B16-BL6 cells after silencing of IDO2 was measured by wound healing assay and Transwell cell migration assay.The invasion ability of the tumor cells was detected by Transwell cell invasion assay.RESULTS:IDO2-siRNA significantly down-regulated IDO2 expression in B16-BL6 melanoma cells,and did not affect IDO1 expression.Compared with control group,the colony formation ability,the migratory distance measured by wound healing assay,and the migration and the invasion cell numbers detected by Transwell assay all remarkably decreased in the IDO2-silencing cells.CONCLUSION:IDO2 silencing affects the proliferation,migration and invasion abilities of the R16-BL6 melanoma cells.