TUMOR-NECROSIS-FACTOR RECEPTOR GENE-EXPRESSION AND SHEDDING IN HUMAN WHOLE LUNG-TISSUE AND PULMONARY EPITHELIUM

This study aimed to investigate the expression of tumour necrosis fact or receptor (TNF-R) at the gene and surface level, and its shedding in human lung tissue and a pulmonary epithelial cell line, A549. Levels of gene expression of TNF-R were evaluated by Northern blot analysis, Human lung tissue expressed both type I and type II TNF-R gene, while A549 cells expressed only type I TNF-R gene. Phorbol ester upregulated and TNF-alpha downregulated the TNF-R gene expression in A549 cells, Consistent with these modulations of TNF-R gene expression, I-125-TNF binding capacities were increased with phorbol ester stimulation and d ecreased with TNF stimulation after 24 h in A549 cells, The shedding o f TNF-R from A549 cells was investigated using enzyme-linked immunosor bent assay (ELISA) for soluble type I TNF-R, Not only lung tissues but also A549 cells spontaneously released soluble type I TNF-R into the culture medium, Both phorbol ester and TNF stimulation accelerated the shedding of soluble TNF-R from A549 cells. These results suggest that type I TNF-R gene expression and shedding of soluble TNF-R are differ entially regulated in A549 cells, We conclude that tumour necrosis fac tor receptor surface expression is regulated, at least in part, at the gene expression level and shedding of soluble tumour necrosis factor receptor is modulated by inflammatory mediators, such as tumour necros is factor in A549 cells.