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TNF alpha down-regulates CD105 expression in vascular endothelial cells: a comparative study with TGF beta 1
Chenggang Li1, Baoqiang Guo, Shigang Ding
1Department of Pathology, Medical School, University of Manchester, Manchester M13 9PT, U.K.
Anticancer Research
|June 25, 2003
Summary
Tumor necrosis factor-alpha (TNF alpha) suppresses CD105 protein levels in endothelial cells, while transforming growth factor-beta 1 (TGF beta 1) increases them. These cytokines have opposing effects on CD105 expression, impacting vascular cell functions.
Area of Science:
- Endothelial cell biology
- Cytokine signaling
- Molecular mechanisms of inflammation
Background:
- Vascular endothelium plays key roles in angiogenesis, inflammation, and immune responses, modulated by cytokines like TNF alpha and TGF beta 1.
- CD105, a TGF beta receptor component, is upregulated in activated endothelium and implicated in inflammatory disorders like rheumatoid arthritis.
- TNF alpha (pro-inflammatory) and TGF beta 1 (anti-inflammatory) regulate crucial cellular processes.
Purpose of the Study:
- To investigate the hypothesis that CD105 gene expression in endothelial cells is regulated by TNF alpha and TGF beta 1.
- To elucidate the opposing roles of these cytokines in modulating CD105 expression.
Main Methods:
- Treatment of human dermal microvascular endothelial cells with varying concentrations and durations of TNF alpha and TGF beta 1.
- Quantification of CD105 protein and mRNA levels.
- Assessment of CD105 promoter activity.
- Evaluation of NF kappa B pathway involvement using PDTC.
Main Results:
- TNF alpha significantly suppressed CD105 protein levels in a concentration- and time-dependent manner (over 50% reduction).
- TNF alpha did not alter CD105 mRNA levels or promoter activity, suggesting post-transcriptional regulation.
- TGF beta 1 significantly increased both CD105 protein and mRNA expression (approx. 2-fold increase) via promoter activation.
Conclusions:
- TNF alpha and TGF beta 1 exert opposing regulatory effects on CD105 expression in human vascular endothelial cells.
- CD105 expression is intricately linked to cytokine-mediated signaling pathways that control cellular functions.