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Intracellular interleukin 6 mediates platelet-derived growth factor-induced proliferation of nontransformed cells
1Department of Internal Medicine and Research, University Hospital Basel, Switzerland.
Abstract:
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.
Insights
Platelet-derived growth factor (PDGF) stimulates cell growth by inducing interleukin 6 (IL-6). Blocking intracellular IL-6 with antisense oligonucleotides inhibited PDGF-induced cell division and key cell cycle gene transcription.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Platelet-derived growth factor (PDGF) is a key regulator of cell growth and proliferation.
- Interleukin 6 (IL-6) is a cytokine with diverse roles in cellular processes, including inflammation and cell growth.
Purpose of the Study:
- To investigate the functional role of interleukin 6 (IL-6) in platelet-derived growth factor (PDGF)-induced cell proliferation.
- To determine if intracellular IL-6 mediates PDGF-induced cell cycle progression.
Main Methods:
- Utilized human fibroblasts, vascular smooth muscle cells, and mesangial cells in culture.
- Administered PDGF isoforms (PDGF-AA, -AB, -BB) and IL-6 antisense oligonucleotides.
- Assessed IL-6 gene expression, protein production, secretion, and cell proliferation.
- Measured transcription of cell cycle-dependent genes (CDC2, PCNA).
Main Results:
- PDGF isoforms induced IL-6 gene expression and cell proliferation in all cell types.
- IL-6 antisense oligonucleotides significantly reduced PDGF-induced IL-6 transcription, translation, and secretion.
- While anti-IL-6 antibodies did not affect proliferation, IL-6 antisense oligonucleotides inhibited cell division.
- IL-6 antisense oligonucleotides abolished PDGF-induced transcription of CDC2 and PCNA genes.
Conclusions:
- Intracellular interleukin 6 (IL-6) plays a critical role in mediating platelet-derived growth factor (PDGF)-dependent proliferation of nontransformed cells.
- PDGF-induced cell cycle progression is dependent on IL-6 signaling, impacting key cell cycle regulators like CDC2 and PCNA.