IL‐10 induces mesangial cell proliferation via a PDGF‐dependent mechanism

Summary 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‐α and β 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.