ArticleMolecular medicine (Cambridge, Mass.)2022
OR2AT4 and OR1A2 counterregulate molecular pathophysiological processes of steroid-resistant inflammatory lung diseases in human alveolar macrophages.
Article in Molecular medicine (Cambridge, Mass.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Cooperation between Adh and OR5M11 contributes to the lung pathogenicity of Actinobacillus pleuropneumoniae by facilitating the NLRP3-mediated inflammatory response.Veterinary research · 2026Article
- Ectopic Olfactory Receptors in Oral Health and Disease: Molecular Links Between Chemosensing, Tissue Repair, Inflammation, and Cancer.International journal of molecular sciences · 2026Review
- Chemosensor receptors are lipid-detecting regulators of macrophage function in cancer.Nature immunology · 2025Article
- Exploring Therapeutic Potential of Bi-Qi Capsules in Treatment of Gout by Discovering Crucial Drug Targets.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Roles of sensory receptors in non-sensory organs: the kidney and beyond.Nature reviews. Nephrology · 2025Review
- A review of research advances in the modulation of olfactory receptors for COPD inflammation and airway remodeling.Frontiers in immunology · 2025Review
- Functional characterization of OR51B5 and OR1G1 in human lung epithelial cells as potential drug targets for non-type 2 lung diseases.Cell biology and toxicology · 2024Article
- Article
- Interkingdom Detection of Bacterial Quorum-Sensing Molecules by Mammalian Taste Receptors.Microorganisms · 2023Review
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTherapeutic options for steroid-resistant non-type 2 inflammation in obstructive lung diseases are lacking. Alveolar macrophages are central in the progression of these diseases by releasing proinflammatory cytokines, making them promising targets for new therapeutic approaches. Extra nasal expressed olfactory receptors (ORs) mediate various cellular processes, but clinical data are lacking. This work investigates whether ORs in human primary alveolar macrophages could impact pathophysiological processes and could be considered as therapeutic targets.
methodsHuman primary alveolar macrophages were isolated from bronchoalveolar lavages of 50 patients with pulmonary diseases. The expression of ORs was validated using RT-PCR, immunocytochemical staining, and Western blot. Changes in intracellular calcium levels were analyzed in real-time by calcium imaging. A luminescent assay was used to measure the cAMP concentration after OR stimulation. Cytokine secretion was measured in cell supernatants 24 h after stimulation by ELISA. Phagocytic ability was measured by the uptake of fluorescent-labeled beads by flow cytometry.
resultsWe demonstrated the expression of functional OR2AT4 and OR1A2 on mRNA and protein levels. Both ORs were primarily located in the plasma membrane. Stimulation with Sandalore, the ligand of OR2AT4, and Citronellal, the ligand of OR1A2, triggered a transient increase of intracellular calcium and cAMP. In the case of Sandalore, this calcium increase was based on a cAMP-dependent signaling pathway. Stimulation of alveolar macrophages with Sandalore and Citronellal reduced phagocytic capacity and release of proinflammatory cytokines.
conclusionThese are the first indications for utilizing olfactory receptors as therapeutic target molecules in treating steroid-resistant lung diseases with non-type 2 inflammation.
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