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TNFα down-regulates CD105 expression in vascular endothelial cells: a comparative study with TGFß1

Li, Chenggang and Guo, Baoqiang and Ding, Shigang and Ruis, Carlos and Langa, Carmen and Kumar, Patricia and Bernabeu, Carmelo and Kumar, Shant (2003) TNFα down-regulates CD105 expression in vascular endothelial cells: a comparative study with TGFß1. ISSN 0250-7005

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Abstract

The vascular endothelium participates in angiogenesis, inflammation and the immune response, which are modulated by vasoactive cytokines such as tumour necrosis factor-α (TNFα) and transforming growth factor-ß1 (TGFß1). CD105 is a component of the TGFß receptor complex and is abundantly expressed in activated/injured endothelium where it is implicated in multiple cellular processes. Up-regulation of CD105 in synovial cells of rheumatoid arthritis and psoriatic lesions implies a possible role in the pathogenesis of such inflammatory disorders. The pro-inflammatory cytokine, TNFα, and anti-inflammatory cytokine, TGFß1, regulate multiple cellular processes such as proliferation, differentiation and apoptosis. Our hypothesis is that CD105 gene expression in endothelial cells is regulated by the multifunctional cytokines TNFα and TGFß1. By using human dermal microvascular endothelial cells the present study has shown that long-term treatment with TNFα (0.1-5 ng/ml) elicited a concentration- and time-dependent significant suppression (over 50% reduction) in CD105 protein levels. The observations that no significant alterations in the CD105 mRNA levels or in the CD105 promoter activity were found and that the potent inhibitor of NFÎB, PDTC, did not affect the TNFα action suggest that CD105 down-regulation by TNF· is not at the transcriptional level. In contrast to TNFα, TGFß1 significantly elevated CD105 protein and mRNA expression (<2-fold increase) through activation of its promoter activity. From these data we conclude that TNFα and TGFß1 exert opposing effects on CD105 expression in human vascular endothelial cells and that CD105 is enmeshed in the network of signal pathways modulating multiple cellular functions.

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