The Expression And Significance Of IL-25 In Rheumatoid Arthritis

Objective To detect the serum levels of IL-25 and IL-17 in rheumatoid arthritis(RA)and investigate the potential relationship with bone erosion and concomitant interstitial lung disease(ILD).To study the function of IL-25 for rheumatoid arthritis(RA)fibroblast-like synoviocytes(FLS)differentiation as well as to the effects on the expression of extracellular regulating protein kinase(ERK)and matrix metalloproteinases-3(MMP-3).Methods A total of 117 RA patients were enrolled act as experiment group,and healthy control selected 56 healthy subjects.The serum levels of IL-25 and IL-17 were determined by ELISA,and RF was detected by turbidimetric immunoassay,anti-CCP antibody as well as ESR and CRP were also tested.Interstitial lung disease(ILD)was identified on high-resolution computed tomography(HR-CT),the degree of bone erosion was inspected by Musculoskeletal ultrasoum examination,and radiographic grade was graded by Sharp-van der Heijde Score(SHS),Disease activity in RA was scored with the DAS28 and visual analogue scale(VAS).the relationship between IL-25 and IL-17 in different groups were evaluated by correlation analysis.The differences on ERK1/2 and MMP-3 protein levels were tested in RA-FLS and healthy controls,then IL-17A(10ng/ml),different concentrations of IL-25(0.01,0.1,1 and 10ng/ml)and IL-17A(10ng/ml)to co-stimulate the RA-FLS for 24 hours respectively,and the expression of ERK1/2 and MMP-3 protein were testted by the Wesern blot.Results(1)The serum levels of IL-25 and IL-17 were increased significantly in patients with RA compared with heathy control group(P<0.01).(2)Compared with bone erosion negative group,the serum level of IL-25 was increased significantly in bone erosion group(P<0.05).(3)The level of IL-25 was higher in the ILD group of RA patients than the non-ILD group(P<0.01).(4)In addition,there was positive correlation between the serum level of IL-25 and RF classification(r=0.367,r=0.319,r=0.436)(P<0.01).Meanwhile,the serum level of IL-17 has the same outcome(r=0.216,r=0.271)(P<0.01),even if they have no correlation with anti-CCP antibody(P>0.05).(5)The expression of ERK1/2 and MMP-3 proteins in RA-FLS was higher than the healthy controls(P<0.01).(6)IL-17 A can stimulate the expression of ERK1/2 and MMP-3proteins in RA-FLS.with the increasion of the concentration on IL-25,the level of ERK1/2 and MMP-3 in RA-FLS which stimulated by IL-17 A was decreased slowly(P<0.01).Conclusion(1)The serum level of IL-25 was higher in RA and rheumatoid arthritis with bone erosion and interstitial lung disease than healthy controls.there was positive correlation between the serum level of IL-25 and RF classification imply that IL-25 may closely associated with rheumatoid arthritis.(2)IL-25 can inhibit the stimulation of IL-17 A on ERK1/2 and MMP-3in RA-FLS fractionally,which prompt that it may take part in the development of RA through this pathway and can play as a target for the treatment on RA.