STIMULATED KIDNEY TUBULAR EPITHELIAL-CELLS EXPRESS MEMBRANE-ASSOCIATED AND SECRETED TNF-ALPHA
STIMULATED KIDNEY TUBULAR EPITHELIAL-CELLS EXPRESS MEMBRANE-ASSOCIATED AND SECRETED TNF-ALPHA
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DOI：
10.1038/ki.1991.201
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发表时间：
1991-08-01
影响因子：
19.6
通讯作者：
KELLEY, VER
中科院分区：
文献类型：
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作者：
JEVNIKAR, AM;BRENNAN, DC;KELLEY, VER
肿瘤坏死因子-α（TNF-α）是一种多效的促炎肽细胞因子，其促进免疫性肾损伤，并参与T细胞活化。 它由巨噬细胞、T细胞和一些非造血细胞产生，并且在皮克量下具有细胞毒性。 由于肾小管上皮细胞（TEC）携带MHCII（Ia）类抗原和粘附分子（ICAM-1）可作为免疫辅助细胞，TEC产生共刺激细胞因子的能力可增强TEC在体内的辅助能力。 我们报告说，转化TEC表达低水平的TNF-α响应于LPS或IL-1-α作为分泌产物和作为细胞毒性膜相关分子显示在细胞表面上。 TEC的表面标记和免疫沉淀研究检测到许多条带，包括突出的26 kD蛋白，其是TNF-α前体的预测大小。 在注射LPS的C3 H/FeJ小鼠的皮质小管中通过原位杂交也检测到TNF-α mRNA转录物，证明了正常肾小管上皮细胞在体内表达TNF-α的能力。 本报告首次证明了肾小管细胞表达TNF-α蛋白的能力，并且膜相关TNF-α不限于造血细胞。 肾小管细胞表面上显示的少量TNF的功能可以通过肾皮质内这些细胞的丰度来放大，并且可以允许TEC在炎症期间调节肾脏内的免疫应答。
Tumor necrosis factor-alpha (TNF-alpha) 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 TNF-alpha in response to LPS or IL-1-alpha as a secreted product and as a cytotoxic membrane associated molecule displayed on the cell surface. Surface labelling and immunoprecipitation studies of TEC detect a number of bands including a prominent 26 kD protein, which is the predicted size of TNF-alpha precursor. TNF-alpha 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 TNF-alpha in vivo. This report demonstrates for the first time the ability of kidney tubular cells to express TNF-alpha protein and that membrane associated TNF-alpha 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.