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摘要
The inflammation-dependent adhesion molecule expressions are characterized in cardiovascular diseases and myocardial tissue infiltrations. Several pro-inflammatory cytokines are elevated in the acute myocardial injury and infarction. Tumor necrosis factor (TNF-alpha), a pro inflammatory cytokine, is raised in the injury tissues and inflammatory regions and involved in the pathogenesis of cardiac injury, inflammation, and apoptosis. In fibroblasts, TNF-alpha-triggered expression of vascular cell adhesion molecule (VCAM)-1 aggravated the heart inflammation. However, the mechanisms underlying TNF-alpha-mediated VCAM-1 expression in cardiac fibroblasts remain unclear. Here, the primary cultured human cardiac fibroblasts (HCFs) were used to investigate the effects of TNF-alpha on VCAM-1 expression. The molecular evidence, including protein, mRNA, and promoter analyses, indicated that TNF-alpha-induced VCAM-1 gene expression is mediated through the TNFR-dependent manner. Activation of TNF-alpha/TNFR system triggered PKC alpha-dependent NADPH oxidase (Nox)/reactive oxygen species (ROS) signal linking to MAPK cascades, and then led to activation of the transcription factor, AP-1. Moreover, the results of mRNA and promoter assay demonstrated that c-Jun/AP-1 phosphorylated by TNF-alpha turns on VCAM-1 gene expression. Subsequently, up regulated VCAM-1 on the cell surface of TNF-alpha-challenged HCFs increased the number of monocytes adhering to these cells. These results indicated that in HCFs, activation of AP-1 by PKC alpha-dependent Nox/ROS/MAPKs cascades is required for TNF-alpha-induced VCAM-1 expression. To clarify the mechanisms of TNF-alpha-induced VCAM-1 expression in HCFs may provide therapeutic strategies for heart injury and inflammatory diseases.
- 出版日期2016-1-28
- 单位长春大学
