title: Transforming growth factor-beta 1 regulates chemokine and complement production by human proximal tubular epithelial cells.
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.
authors.affiliation: Department of Nephrology, Leiden University Hospital, The Netherlands.
authors.forename: J S
authors.initials: JS
authors.lastname: Gerritsma
authors.forename: C
authors.initials: C
authors.lastname: van Kooten
authors.forename: A F
authors.initials: AF
authors.lastname: Gerritsen
authors.forename: L A
authors.initials: LA
authors.lastname: van Es
authors.forename: M R
authors.initials: MR
authors.lastname: Daha
mesh_terms: 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*
chemical_list: 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