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Regulatory effect of prostaglandin E2 on fibronectin release from human alveolar macrophages
T Ozaki1, H Moriguchi, Y Nakamura
1Third Department of Internal Medicine, School of Medicine, Tokushima University, Japan.
Abstract:
Fibronectin (Fn), which is released from several kinds of cells including alveolar macrophages (AM), is important in inflammatory reactions in the certain lung diseases such as idiopathic pulmonary fibrosis (IPF). Therefore, information on the mechanisms regulating Fn release from AM may be useful for elucidating the pathogenesis of these diseases and developing therapeutic modalities. We supposed that prostaglandin E2 (PGE2), which is known to modulate cellular functions, might be involved in regulation of Fn release, and, accordingly, we measured the release of Fn and PGE2 from AM from normal volunteers (NV), control patients (CP), and patients with IPF. AM from patients with IPF were found to release more Fn than AM from NV (IPF: 250 +/- 58.8/10(6) cells.24 h, NV: 53.0 +/- 7.3 ng/10(6) cells.24 h) and to release less PGE2 than the latter (IPF: 0.48 +/- 0.12 ng/10(6) cells.24 h, NV:1.35 +/- 0.24 ng/10(6) cells.24 h). A negative correlation was found between the contents of Fn and PGE2 in the culture media of AM from NV, CP, and patients with IPF. Lipopolysaccharide, phorbol myristate acetate, and zymosan suppressed Fn release from AM but stimulated their PGE2 release, and these effects were reversed by indomethacin. Exogenous PGE2 (greater than 1 x 10(-8) M) suppressed Fn release. The albumin-antialbumin complex stimulated Fn release but did not affect PGE2 release. These results indicate that Fn release from AM changed in response to various stimuli, and that PGE2 is important in suppressing Fn release from AM, suggesting a negative feedback mechanism of PGE2 in releasing Fn.
Insights
Fibronectin (Fn) release from alveolar macrophages (AM) is elevated in idiopathic pulmonary fibrosis (IPF). Prostaglandin E2 (PGE2) suppresses Fn release, suggesting a negative feedback mechanism crucial for lung disease pathogenesis.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Immunology
Background:
- Fibronectin (Fn) is integral to inflammatory responses in lung diseases like idiopathic pulmonary fibrosis (IPF).
- Alveolar macrophages (AM) are a source of Fn, making their regulatory mechanisms key to understanding IPF pathogenesis.
- Prostaglandin E2 (PGE2) is known to modulate cellular functions, suggesting a potential role in Fn regulation.
Purpose of the Study:
- To investigate the role of prostaglandin E2 (PGE2) in regulating fibronectin (Fn) release from alveolar macrophages (AM).
- To compare Fn and PGE2 release from AM in normal volunteers (NV), control patients (CP), and patients with IPF.
- To elucidate the mechanisms underlying Fn release from AM in the context of lung diseases.
Main Methods:
- Quantification of Fn and PGE2 release from AM obtained from NV, CP, and IPF patients.
- Assessment of the effects of various stimuli (lipopolysaccharide, phorbol myristate acetate, zymosan, albumin-antialbumin complex) on Fn and PGE2 release.
- Investigation of the impact of indomethacin and exogenous PGE2 on Fn and PGE2 release.
Main Results:
- AM from IPF patients released significantly more Fn and less PGE2 compared to AM from NV.
- A negative correlation was observed between Fn and PGE2 levels in AM cultures from all groups.
- Stimuli like LPS, PMA, and zymosan suppressed Fn release while increasing PGE2 release, effects reversed by indomethacin; exogenous PGE2 inhibited Fn release.
Conclusions:
- Prostaglandin E2 plays a critical role in suppressing fibronectin release from alveolar macrophages.
- A negative feedback mechanism involving PGE2 is suggested to regulate Fn release from AM.
- Understanding this PGE2-mediated regulation offers potential therapeutic targets for fibrotic lung diseases.