Transforming growth factor-beta 1 regulates chemokine and complement production by human proximal tubular epithelial cells

Kidney Int. 1998 Mar;53(3):609-16. doi: 10.1046/j.1523-1755.1998.00799.x.

Abstract

Previously it has been demonstrated that human proximal tubular epithelial cells (PTEC) are able to produce chemokines (such as IL-8 and MCP-1) and complement components (such as C2, C3, C4 and factor H), and that production of these proteins is regulated by pro-inflammatory cytokines such as interleukin-1 alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). Since TGF-beta is also expressed in the renal interstitium during inflammation, we investigated the effect of TGF-beta on the production of chemokines and complement components by PTEC in culture. Transforming growth factor-beta 1 up-regulated IL-8 production by an average of 4.17 +/- 1.0 fold. macrophage chemoattractant phagocyte (MCP-1) production, on the other hand, was down-regulated by TGF-beta 1 by an average of 2.2 +/- 0.7 fold. The production of C3 and C4 was also down-regulated after incubation with TGF-beta 1 (1.9 +/- 0.3- and 3.0 +/- 1.2-fold, respectively). All effects were dose- and time-dependent and were found to be specific for TGF-beta 1, as assessed by inhibition of the effect with a neutralizing antibody against TGF-beta 1. These data, together with the knowledge that TGF-beta, chemokines and complement components play a role in several types of renal disease, suggest that TGF-beta is involved in the regulation of local expression of chemokines and complement components by tubular cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Cell Line
  • Chemokine CCL2 / biosynthesis
  • Chemokines / biosynthesis*
  • Complement C3 / biosynthesis
  • Complement C4 / biosynthesis
  • Complement System Proteins / biosynthesis*
  • Dose-Response Relationship, Drug
  • Humans
  • Interleukin-8 / biosynthesis
  • Kidney Diseases / etiology
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / immunology*
  • Kinetics
  • Transforming Growth Factor beta / administration & dosage
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Antibodies, Monoclonal
  • Chemokine CCL2
  • Chemokines
  • Complement C3
  • Complement C4
  • Interleukin-8
  • Transforming Growth Factor beta
  • Complement System Proteins