Objective To investigate the mechanism of endothelin (ET) inflammatory effects on human mesangial cells (HMC). Methods The following experiments were performed on cultured HMC after ET-1 stimulation: (1) the expression of tumor necrosis factor-α (TNFα) , interleukin-1β (IL-1β), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelin-1 (ET-1) itself messenger ribonucleic acid (mRNA) was determined by Northern Blot analysis; (2) the TNFα concentration -was tested with radioimmunoassay; the IL-1 activity was assayed by the enhancement of thymocyte proliferation in response to mitogen; the surface expression of ICAM-1 and VCAM-1 was measured with cell emzyme linked immunoadsorbent assay (ELISA) analysis. Results ET-1 (10-7mol/L) induced the following changes on HMC: (1) up-regulation of the expression of TNFα mRNA and protein; (2) up-regulation of the expression of ICAM-1 and VCAM-1 mRNA and protein; (3) up-regulation of the expression of ET-1 itself mRNA. However, the expression of IL-1 mRNA and protein was not changed. Conclusions ET-1 can stimulate HMC to produce TNFα, ICAM-1 and VCAM-1, and there by induce inflammatory effects. ET-1 can also stimulate HMC to up-regulate the expression of ET-1 itself, so as to amplify inflammatory effects. So, ET-1 is actually an inflammatory mediator and may play an important role in the pathogenesis of glomerulonephritis.
ASJC Scopus subject areas