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A molecular basis of cell death in olfactory epithelium
A I Farbman1, J A Buchholz, Y Suzuki
1Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208-3520, USA. afarbman@nwu.edu
Abstract:
When the membrane receptor Fas binds its ligand, Fas ligand (FasL), an apoptotic cascade is initiated in the cell bearing the Fas receptor. The same can be said about the tumor necrosis factor receptor-1 (TNFR1) and its ligand, TNF-alpha. In this study we have shown that the mRNAs of both sets of ligands and receptors, Fas/FasL and TNF-alpha/TNFR1, were present in unperturbed olfactory epithelium. Fas and FasL were shown by immunohistochemistry and by Western blots of bulbectomized animals to be in the neurons and in some non-neuronal (microvillar) cells of unperturbed rat olfactory epithelium. Addition of either FasL or TNF-alpha to organotypic cultures of fetal rat olfactory epithelium resulted in a significant increase in the number of apoptotic bodies after 4-6 hours. These data raise the possibility that either or both ligand-receptor pairs participate in cell death in the olfactory epithelium.
Insights
The olfactory epithelium expresses Fas/FasL and TNF-alpha/TNFR1. Activating these pathways with Fas ligand or TNF-alpha increases apoptosis in olfactory epithelium cultures, suggesting their role in cell death.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- The Fas receptor/Fas ligand (FasL) and tumor necrosis factor receptor-1 (TNFR1)/TNF-alpha pathways are known initiators of apoptosis.
- The olfactory epithelium is a complex sensory tissue with ongoing cell turnover.
Purpose of the Study:
- To investigate the presence and potential role of Fas/FasL and TNF-alpha/TNFR1 signaling in the rat olfactory epithelium.
- To determine if these pathways can induce apoptosis in olfactory epithelium cultures.
Main Methods:
- Immunohistochemistry and Western blotting were used to detect Fas and FasL expression in rat olfactory epithelium.
- Organotypic cultures of fetal rat olfactory epithelium were treated with FasL or TNF-alpha.
- Apoptotic bodies were quantified after treatment.
Main Results:
- mRNA for Fas/FasL and TNF-alpha/TNFR1 were detected in the unperturbed olfactory epithelium.
- Fas and FasL proteins were localized to neurons and microvillar cells.
- Exposure to FasL or TNF-alpha significantly increased apoptotic bodies in cultured olfactory epithelium.
Conclusions:
- The Fas/FasL and TNF-alpha/TNFR1 signaling pathways are expressed in the rat olfactory epithelium.
- These pathways are capable of inducing apoptosis in olfactory epithelium cells.
- Fas/FasL and TNF-alpha/TNFR1 may play a role in regulating cell death within the olfactory epithelium.
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