ABSTRACT
OBJECTIVES: This study investigates the role of TNF-induced protein 3 (TNFAIP3) and CCAAT/enhancer-binding protein ß (C/EBPß) in alveolar macrophages (AMs) of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) and their influence on pulmonary fibrosis. METHODS: Transfection of HEK293T cells and AMs with plasmids carrying TNFAIP3 and C/EBPß was performed, followed by co-culturing AMs with pulmonary fibroblasts. Immunoblotting analysis was then utilized to assess the expression of TNFAIP3, C/EBPß, and collagen type 1 (Col1). Quantitative PCR analysis was conducted to quantify the mRNA levels of C/EBPß, IL-10, and TGF-ß1. STRING database analysis, and immunoprecipitation assays were employed to investigate the interactions between TNFAIP3 and C/EBPß. RESULTS: TNFAIP3 expression was significantly reduced in SSc-ILD AMs, correlating with increased Col1 production in fibroblasts. Overexpression of TNFAIP3 inhibited this pro-fibrotic activity. Conversely, C/EBPß expression was elevated in SSc-ILD AMs, and its reduction through TNFAIP3 restoration decreased pro-fibrotic cytokines IL-10 and TGFß1 levels. Protein-protein interaction studies confirmed the regulatory relationship between TNFAIP3 and C/EBPß. CONCLUSIONS: This study highlights the important role of TNFAIP3 in regulating pulmonary fibrosis in SSc-ILD by modulating C/EBPß expression in AMs. These findings suggest that targeting TNFAIP3 could be a potential therapeutic strategy for managing SSc-ILD patients.
Subject(s)
CCAAT-Enhancer-Binding Protein-beta , Coculture Techniques , Fibroblasts , Lung Diseases, Interstitial , Macrophages, Alveolar , Scleroderma, Systemic , Tumor Necrosis Factor alpha-Induced Protein 3 , Female , Humans , Male , Middle Aged , CCAAT-Enhancer-Binding Protein-beta/metabolism , CCAAT-Enhancer-Binding Protein-beta/genetics , Collagen Type I/metabolism , Collagen Type I/genetics , Fibroblasts/metabolism , HEK293 Cells , Interleukin-10/metabolism , Interleukin-10/genetics , Lung/metabolism , Lung/pathology , Lung Diseases, Interstitial/metabolism , Lung Diseases, Interstitial/etiology , Macrophages, Alveolar/metabolism , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/etiology , Scleroderma, Systemic/metabolism , Scleroderma, Systemic/complications , Signal Transduction , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor alpha-Induced Protein 3/metabolism , Tumor Necrosis Factor alpha-Induced Protein 3/genetics , Adult , AgedABSTRACT
Objective To evaluate the efficacy and safety of glucosamine (GS) combined with chondroitin sulfate (CS) for knee osteoarthritis (OA).Methods We searched the CENTRAL (Issue 1,2016),PUBMED (1946 to 2016.1.20),EMBASE (1947 to 2016.1.20),CBM (1978 to 2016.1.20),CNKI (1994 to 2016.1.20),WanFang Data (1980 to 2016.1.20) and VIP (1989 to 2016.1.20) and we searched randomized controlled trials (RCT) of GS combined with CS for knee OA.Two reviewers independently identified the included trials,evaluated the quality of methodology and extracted data.The Review manager 5.3 software was used for data analysis.Results Four RCTs were included in this systematic review.The combination group compared with GS group,a total number of 1 145 patients,and the combination group compared with CS group,a total number of 1 067 patients.The outcomes showed:① Among those 4 RCTs that comparing the combination with GS,three RCTs reported western ontario and mcmaster universities osteoarthritis index (WOMAC) score.Summarized results of these 3 RCTs showed no significant difference between combination group and GS group (all P values ＞0.05).MDs of WOMAC score in pain,stiffnessand function were-6.60[95％CI(-18.79,5.59),-15.90(-43.09,11.29) and-6.44 (-16.46,3.59)].② Two long-term (≥6 months) study (n=937) compared the combination with CS group and showed no significant difference (all P values ＞0.05).Pooled MD of WOMAC score in pain and function were-0.80 (-4.96,3.36) and-1.76 (-4.46,0.94) respectively.③ Subgroup analysis in 1 RCT showed that in moderate-to-severe knee pain group (n=142) combination obviously improve the WOMAC score in pain,stiffnessand function compared with CS groupand the differences werestatistically significant (all P values ＜0.05).MDs were-10.46(-17.98,-2.94),-9.70(-18.48,0.92) and 9.39 (-17.33,-1.45).Conclusion There is no evidence to support that the combination of GS and CS for knee OA cansignificantlyimprovethe WOMAC score compared with either GS or CS.For patients with-moderate-to-severe knee pain,combination might be superior toeither GS or CS.
