Stimulated kidney tubular epithelial cells express membrane associated and secreted TNFα

Tumor necrosis factor-alpha (TNFα) is a pleiotropic, pro-inflammatory peptide cytokine which promotes immune renal injury, and participates in T cell activation. It is produced by macrophages, T cells, and some non-hematopoietic cells, and is cytotoxic in picogram quantities. As renal tubular epithelial cells (TEC) bearing MHC class II (Ia) antigens and adhesion molecules (ICAM-1) can act as immune accessory cells, the ability of TEC to produce costimulatory cytokines could augment TEC accessory capacity in vivo. We report that transformed TEC express low levels of TNFα in response to LPS or IL-1α as a secreted product and as a cytotoxic membrane associated molecule displayed on the cell surface. Surface labelling and immuno-precipitation studies of TEC detect a number of bands including a prominent 26 kD protein, which is the predicted size of TNFα precursor. TNFα mRNA transcripts were also detected by in situ hybridization in cortical tubules of C3H/FeJ mice injected with LPS, demonstrating the capacity of normal tubular epithelial cells to express TNFα in vivo. This report demonstrates for the first time the ability of kidney tubular cells to express TNFα protein and that membrane associated TNFα is not limited to hematopoietic cells. The function of small amounts of TNF displayed on the surface of tubular cells may be amplified by the abundance of these cells within the renal cortex, and may allow TEC to modulate immune responses within the kidney during inflammation.