Study Of The Effect Of IL-26 On Proliferation And Apoptosis Of Fibroblastic Synoviocytes And Its Mechanism Of Action

ObjectiveRheumatoid arthritis is a disease with a high disability rate.Excessive proliferation of synovial cells is the core factor that leads to the occurrence and development of the disease.There are many factors that can lead to the proliferation and apoptosis of synovial cells,one of which is the effect of inflammatory factors.IL-26 is an inflammatory factor belonging to the IL-10 family.Studies have shown that IL-26 is significantly elevated in the serum of patients with rheumatoid arthritis,but the effect of IL-26 on the proliferation and apoptosis of synovial cells of rheumatoid arthritis has not been studied.This research sought to explore the influence and process of IL-26 on the proliferation and death of synovial cells in rheumatoid arthritis.MethodsRheumatoid arthritis fibroblast-like synoviocytes(RAFLS)were cultured in vitro,and then added 0,1,10,and 20ng/ Ml L-26 to collect and incubate for 48 hours.At varying concentrations,cells proliferated and apoptosed.After the 20ng/m LIL-26 dose was chosen,the experiment was split into four groups: a blank control,an IL-26 group,an IL-26+STAT1 blocker group,and an IL-26+STAT3 blocker group.The proliferation and apoptosis of different groups of cells were detected.The m RNA expressions of pro-apoptotic protein BAX and anti-apoptotic protein Bcl2 were identified,as well as RAFLS levels of both proteins.Results(1)The effect of IL-26 on the proliferation of RAFLS: Compared with the blank control group,the cell proliferation level increased with the increase of IL-26 concentration,and the cell proliferation level increased most obviously when the IL-26 concentration was 20ng/ml.(2)The apoptosis of RAFLS was significantly inhibited when the concentration of IL-26 was raised to 20ng/ml,compared to the blank control group.This was the most significant effect of IL-26 on the apoptosis of RAFLS.(3)A comparison of the IL-26 and blank control groups revealed a marked enhancement in cell proliferation;however,STAT1 and STAT3 pathways had a significantly less pronounced effect on IL-26-mediated RAFLS proliferation.Furthermore,the addition of STAT3 blocker caused a significant decrease in cell proliferation in both groups.There was no significant change in cell proliferation after the addition of STAT1 blocker.(4)The effect of STAT1 and STAT3 pathways on the degree of IL-26-mediated apoptosis of RAFLS: compared with the blank control group,the apoptosis of RAFLS was inhibited after the addition of IL-26.The STAT3blocker’s addition caused a marked rise in the apoptosis level of cells when compared to the IL-26 group.There was no significant change in apoptosis after the addition of STAT1 blocker.(5)In RAFLS,BAX m RNA expression was significantly lower in the IL-26 group than in the blank control group,while Bcl2 m RNA expression was notably higher.However,when STAT3 blocker was added,Significant increase in m RNA expression of BAX,but significantly decreased m RNA expression of Bcl 2,The m RNA expressions of BAX and Bcl2 were not significantly decreased or increased after STAT1 blocker was added.(6)The effect of IL-26 on the protein level of apoptosis-related proteins BAX and Bcl 2 in RAFLS: As determined by Western blot experiment,the BAX expression decreased in IL-26 group and the expression of Bcl 2 significantly increased in IL-26 group compared with the blank control group.Compared with the IL-26 group,the expression of Bcl 2 was significantly reduced after the addition of the STAT 3 blocker.The expression of BAX did not change significantly.Both BAX and Bcl 2 expression did not change significantly after the addition of the STAT 1 blocker.ConclusionsIL-26 promotes proliferation and inhibits apoptosis of RAFLS with increasing concentration,and this effect is regulated by the STAT3 pathway independent of the STAT1 pathway.