INTRACELLULAR INTERLEUKIN-6 MEDIATES PLATELET-DERIVED GROWTH FACTOR-INDUCED PROLIFERATION OF NONTRANSFORMED CELLS

The functional relevance of interleukin 6 (IL-6) in platelet-derived g rowth factor (PDGF)-induced cell growth was evaluated in cultures of h uman fibroblasts, vascular smooth muscle cells, and mesangial cells, T he three isoforms of the PDGF-namely, PDGF-AA, -AB, and -BB-induced th e expression of the IL-6 gene and proliferation of the nontransformed cells, PDGF-induced transcription, translation, and secretion of IL-6 were diminished in the presence of IL-6 antisense oligonucleotides. Wh ile neutralizing anti-IL-6 antibodies failed to affect the growth fact or-dependent cell proliferation, IL 6 antisense oligonucleotides inhib ited cell division. In addition, IL-6 antisense oligonucleotides aboli shed PDGF-induced transcription of the genes coding for the cell divis ion cycle 2-related protein (CDC2) and proliferating cell nuclear anti gen (PCNA), both of which are regulated in a cell cycle-dependent mann er, It is concluded that PDGF-dependent proliferation of nontransforme d cells involves the action of intracellular IL-6.