Transforming growth factor-beta 1 regulates chemokine and complement production by human proximal tubular epithelial cells.
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.
Gerritsma
J S
JS
Department of Nephrology, Leiden University Hospital, The Netherlands.
van Kooten
C
C
Gerritsen
A F
AF
van Es
L A
LA
Daha
M R
MR
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis*; D003176:Complement C3 / Q000096:biosynthesis; D003181:Complement C4 / Q000096:biosynthesis; D003165:Complement System Proteins / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D007674:Kidney Diseases / Q000209:etiology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D007700:Kinetics; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D018932:Chemokine CCL2; D018925:Chemokines; D003176:Complement C3; D003181:Complement C4; D016209:Interleukin-8; D016212:Transforming Growth Factor beta; D003165:Complement System Proteins