title: IL-10 induces mesangial cell proliferation via a PDGF-dependent mechanism.
abstract: Interleukin-10 (IL-10) is a mesangial cell growth factor in vivo and in vitro. However, the mechanism by which IL-10 exerts its mitogenic activity is not known. The aim of this study was to determine whether IL-10 induces mesangial cell proliferation in a PDGF-dependent or independent fashion. A well--characterized rat mesangial cell line (1097) was used in a series of cell proliferation experiments in which cells were serum-starved and then incubated with recombinant IL-10 in the presence or absence of STI 571 (a specific inhibitor of signalling via the PDGF-alpha and beta receptors) or a neutralizing anti-PDGF-AB antibody. IL-10 induced significant mesangial cell proliferation at 24 and 48 h after cytokine addition. This response was inhibited totally by the addition of STI-571, demonstrating that IL-10 mitogenic activity has an absolute requirement for signalling through the PDGF receptor. In further studies, it was found that STI-571 could be added 24 h after IL-10 stimulation and still exert a profound inhibition of IL-10 mitogenic activity. The ability of a neutralizing anti-PDGF-AB antibody to inhibit completely IL-10-induced mesangial cell proliferation confirmed that IL-10 acts via induction of an autocrine PDGF response rather than the possibility that IL-10 may transactivate the PDGF receptor in a PDGF-independent fashion. In conclusion, this study has demonstrated that IL-10 induces mesangial cell proliferation via an autocrine PDGF-mediated mechanism. Thus, therapies which antagonize PDGF signalling will also inhibit any contribution of IL-10 to mesangial proliferation.
authors.affiliation: Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: T E
authors.initials: TE
authors.lastname: Robertson
authors.forename: D J
authors.initials: DJ
authors.lastname: Nikolic-Paterson
authors.forename: L A
authors.initials: LA
authors.lastname: Hurst
authors.forename: R C
authors.initials: RC
authors.lastname: Atkins
authors.forename: S J
authors.initials: SJ
authors.lastname: Chadban
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D001549:Benzamides; D002455:Cell Division; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000068877:Imatinib Mesylate; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D016753:Interleukin-10; D000068877:Imatinib Mesylate; D013936:Thymidine