Proinflammatory Cytokines Enhance Cox-1 Gene Expression in Cultured Rat Glomerular Mesangial Cells
Resource
INTERNATIONAL IMMUNOPHARMACOLOGY v.4 n.1 pp.47-56
Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Journal Volume
v.4
Journal Issue
n.1
Pages
47-56
Date Issued
2003
Date
2003
Author(s)
TSAI, CHANG-YU
YU, CHIA-LI
Abstract
Glomerular mesangial cells (GMC) exert an essential maintaining effect on hemodynamic integrity and immune competence of the kidney through arachidonate metabolism. To clarify this, cultured rat GMC were measured for the expression and production of cyclooxygenase (COX) and excretion of prostaglandin (PG). The rat GMC spontaneously expressed type 1 cyclooxygenase (COX-1), but not COX-2. The PGE2 and thromboxane B2 (TXB2) were spontaneously produced by the cells. Interleukin (IL)-1beta (25 ng/ml ), IL-8 (25 ng /ml), growth-related oncogene-alpha (GRO, 50 ng/ml) and tumor necrosis factor-alpha (TNF-alpha, 25 ng/ml) stimulated the COX-1 protein production as demonstrated by Western blot and enhanced PGE2 synthesis in GMC, beginning on 2 h of incubation, and steadily enhanced TXB2 synthesis over a 24- h period. Lipopolysaccharide (LPS, 100 ng/ml) enhanced both PGE2 and TXB2 syntheses from 2 h to at least 24 h of incubation. Collectively, the proinflammatory cytokines could enhance COX- 1 but not COX-2 expression in GMC leading to increased PGE2 and TXB2 production. These biochemical events may be implicated in normal renal physiology as well as in pathogenesis of glomerular diseases. (C) 2003 Elsevier B.V. All rights reserved.
Subjects
arachidonate
cyclooxygenase
eicosanoids
mesangial cells
prostaglandin