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Interferon-gamma modulates lung macrophage production of PDGF-BB and fibroblast growth
A Badgett1, J C Bonner, A R Brody
1Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Abstract:
Platelet-derived growth factor (PDGF) is a potent mediator of fibroblast proliferation and chemotaxis. We have studied here the cytokine interferon-gamma (IFN-gamma) which is known to prime macrophages for increased PDGF production. Thus, we postulated that IFN-gamma would act as a positive regulator of PDGF-BB secretion by rat alveolar macrophages, and in addition we asked whether or not the IFN-gamma (a known anti-mitogenic cytokine) would block the growth response of primary lung fibroblasts to the PDGF-BB. Macrophages incubated with IFN-gamma or iron spheres alone for 24 h secreted 2.5-fold more PDGF-BB than control macrophages incubated in serum-free medium. Preincubation of macrophages with IFN-gamma prior to the addition of iron spheres synergistically increased PDGF-BB production 2-10-fold after 24 h. In contrast, when IFN-gamma was added to quiescent rat lung fibroblasts (RLFs) in the presence of PDGF-BB, the cytokine induced a concentration-dependent decrease in cell growth, while IFN-gamma alone did not affect proliferation. [125I]PDGF-BB receptor assays showed that neither preincubation nor coincubation of RLF with IFN-gamma affected PDGF-BB binding to its receptors.
Insights
Interferon-gamma (IFN-gamma) boosts platelet-derived growth factor (PDGF-BB) secretion by macrophages but inhibits PDGF-BB-induced lung fibroblast growth, without affecting PDGF receptor binding.
Area of Science:
- Cell Biology
- Immunology
- Pulmonary Medicine
Background:
- Platelet-derived growth factor (PDGF) is crucial for fibroblast proliferation and migration.
- Interferon-gamma (IFN-gamma) primes macrophages for enhanced PDGF production.
- The anti-mitogenic role of IFN-gamma in lung fibroblasts warrants investigation.
Purpose of the Study:
- To investigate IFN-gamma's role in regulating PDGF-BB secretion by rat alveolar macrophages.
- To determine if IFN-gamma inhibits PDGF-BB-induced proliferation of rat lung fibroblasts.
- To explore the mechanism of IFN-gamma's effect on PDGF-BB signaling in fibroblasts.
Main Methods:
- Rat alveolar macrophages were treated with IFN-gamma and/or iron spheres.
- PDGF-BB secretion levels were quantified using ELISAs.
- Rat lung fibroblasts (RLFs) were treated with PDGF-BB and/or IFN-gamma.
- Fibroblast proliferation was assessed using cell counting assays.
- [125I]PDGF-BB binding assays were performed to evaluate receptor interaction.
Main Results:
- IFN-gamma alone increased PDGF-BB secretion by 2.5-fold in macrophages.
- Combined IFN-gamma and iron sphere treatment synergistically increased PDGF-BB production 2-10 fold.
- IFN-gamma inhibited PDGF-BB-induced RLF proliferation in a dose-dependent manner.
- IFN-gamma did not affect PDGF-BB binding to its receptors on RLFs.
Conclusions:
- IFN-gamma acts as a positive regulator of PDGF-BB secretion by macrophages.
- IFN-gamma exhibits anti-proliferative effects on lung fibroblasts stimulated by PDGF-BB.
- The anti-mitogenic effect of IFN-gamma on fibroblasts is independent of PDGF receptor binding.