Proinflammatory cytokines enhance COX-1 gene expression in cultured rat glomerular mesangial cells

Int Immunopharmacol. 2004 Jan;4(1):47-56. doi: 10.1016/j.intimp.2003.10.003.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Chemokines / pharmacology
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Dinoprostone / biosynthesis
  • Gene Expression
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / metabolism*
  • Interleukin-1 / pharmacology
  • Interleukin-8 / pharmacology
  • Isoenzymes / biosynthesis*
  • Isoenzymes / genetics
  • Lipopolysaccharides / pharmacology
  • Membrane Proteins
  • Mice
  • Mice, Inbred MRL lpr
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Rats
  • Thromboxane B2 / biosynthesis
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Chemokines
  • Cytokines
  • Interleukin-1
  • Interleukin-8
  • Isoenzymes
  • Lipopolysaccharides
  • Membrane Proteins
  • Tumor Necrosis Factor-alpha
  • Thromboxane B2
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, mouse
  • Ptgs1 protein, rat
  • Dinoprostone