Intracellular interleukin 6 mediates platelet-derived growth factor-induced proliferation of nontransformed cells.
The functional relevance of interleukin 6 (IL-6) in platelet-derived growth factor (PDGF)-induced cell growth was evaluated in cultures of human fibroblasts, vascular smooth muscle cells, and mesangial cells. The three isoforms of the PDGF--namely, PDGF-AA, -AB, and -BB--induced the 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. While neutralizing anti-IL-6 antibodies failed to affect the growth factor-dependent cell proliferation, IL-6 antisense oligonucleotides inhibited cell division. In addition, IL-6 antisense oligonucleotides abolished PDGF-induced transcription of the genes coding for the cell division cycle 2-related protein (CDC2) and proliferating cell nuclear antigen (PCNA), both of which are regulated in a cell cycle-dependent manner. It is concluded that PDGF-dependent proliferation of nontransformed cells involves the action of intracellular IL-6.
Roth
M
M
Department of Internal Medicine and Research, University Hospital Basel, Switzerland.
Nauck
M
M
Tamm
M
M
Perruchoud
A P
AP
Ziesche
R
R
Block
L H
LH
D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013873:Thionucleotides
D015850:Interleukin-6; D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D013873:Thionucleotides; D016203:CDC2 Protein Kinase