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Updated: Sep 29, 2025
Isolation of Lung Retinoid-Containing Cells by Cell Sorting
Published on: April 11, 2025
Retinoid receptors are expressed in mouse and human lungs
Shankaramurthy Channabasappa1, Sarah Caldwell1, Rani Kanthan2
1Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Canada.
Abstract:
Retinoid receptors are members of nuclear receptor superfamily consisting of two distinct families: RARs (retinoic acid receptors) and RXRs (retinoid X receptors). Each family contains three receptor subtypes α, β, and γ. Retinoids transduce their effects through binding to retinoid receptors and inhibit transcription factors such as activator protein-1 and nuclear factor-κB (NF-κB) both of which regulate the transcription of several inflammatory genes. Considering the role of retinoid receptors in lung physiology, we need a precise understanding of their expression in normal and inflamed lungs. We used light and electron microscopic immunohistochemistry and Western blot to determine the expression of retinoid receptors in a murine model of endotoxin-induced (E. coli; 055:B5, 80 μg intranasal) acute lung inflammation and normal human lungs. Western blot showed expression of all six retinoid receptor subtypes in normal and inflamed mouse lungs. Immunohistology localized differential expression of retinoid receptors in airway epithelium, alveolar/septal macrophages, vascular endothelium, and alveolar septum in mouse lungs. Intranasal LPS challenge in mice resulted in increased expression of RXRα in airway epithelium compared to control animals. All six retinoid receptor subtypes were expressed in normal human lungs. Immunoelectron microscopy further confirmed the localization of all the receptors in various lung cells including the nucleus of these cells. The basal and altered expression of retinoid receptors in normal and inflamed lungs, respectively, may suggest their roles in lung pathophysiology.
Insights
Retinoid receptors (RARs and RXRs) are expressed in normal and inflamed lungs. Their altered expression in lung inflammation suggests a role in lung pathophysiology.
Area of Science:
- Molecular Biology
- Cell Biology
- Immunology
Background:
- Retinoid receptors, including retinoic acid receptors (RARs) and retinoid X receptors (RXRs), are nuclear receptors involved in regulating gene transcription.
- Retinoids influence inflammatory pathways by inhibiting transcription factors like activator protein-1 and nuclear factor-κB (NF-κB).
Purpose of the Study:
- To investigate the expression and localization of all six retinoid receptor subtypes (RARα, β, γ and RXRα, β, γ) in normal and inflamed murine lungs.
- To compare retinoid receptor expression in mouse lungs with normal human lungs.
Main Methods:
- Western blot analysis to detect retinoid receptor expression.
- Light and electron microscopic immunohistochemistry to localize retinoid receptors in lung tissues.
- Murine model of endotoxin-induced acute lung inflammation using intranasal lipopolysaccharide (LPS).
Main Results:
- All six retinoid receptor subtypes were detected in both normal and inflamed mouse lungs via Western blot.
- Immunohistology revealed differential localization of retinoid receptors in mouse lung cells, including airway epithelium, macrophages, and endothelium.
- Intranasal LPS challenge led to increased RXRα expression in the airway epithelium of mice.
- All six retinoid receptor subtypes were also found in normal human lungs, with immunoelectron microscopy confirming their presence in various lung cells, including the nucleus.
Conclusions:
- Retinoid receptors are expressed in various cell types within the normal and inflamed lung.
- The basal and altered expression patterns of retinoid receptors in the lung suggest their involvement in lung physiology and pathophysiology, particularly during inflammation.
