Dysregulation of TNF-induced protein 3 and CCAAT/enhancer-binding protein ß in alveolar macrophages: Implications for systemic sclerosis-associated interstitial lung disease.

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.

Role of EGFR as a prognostic factor for survival in head and neck cancer: a meta-analysis.

The prognostic role of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) remains controversial. The goal of this study was to summarize existing evidence regarding whether EGFR overexpression is a prognostic factor in HNSCC. Relevant studies were identified using Pubmed, Ovid, and Web of Science databases. A meta-analysis was conducted on the prognostic value of EGFR expression for overall survival (OS) and disease-free survival (DFS). Thirty-seven studies were included. Primary analysis indicated that EGFR overexpression was associated with reduced OS (hazard ratio [HR]: 1.694, 95% confidence interval [CI]: 1.432­2.004). DFS, on the other hand, was not associated with EGFR expression after adjusting for publication bias (HR: 1.084, 95% CI: 0.910­1.290). Subgroup analysis gave a statistically significant pooled HR for OS in laryngeal carcinoma (HR: 2.519, 95% CI: 1.615­3.928) and in oropharyngeal carcinoma (HR: 2.078, 95% CI: 1.605­2.690). The pooled HR was statistically significant for DFS with respect to oropharyngeal carcinoma (HR: 1.055, 95% CI: 1.020­1.092), but not laryngeal carcinoma (HR: 1.750, 95% CI: 0.911­3.360). When dividing studies based on the immunohistochemistry (IHC) scoring system, only the group that evaluated EGFR expression according to the intensity and extent of staining showed no between-study heterogeneity for both OS and DFS. Overall, EGFR overexpression was associated with shortened OS, but not DFS. Future studies are needed that stratify patients by specific tumor sites. Furthermore, when estimating protein level by the IHC method, it is advisable to consider both intensity and extent of staining.