Biology subjects

Carey, R. M.

Publications and source records attributed to Carey, R. M..

15 recordsLinked to original sources

bioRxiv2026

Targeting cyclic-AMP/phosphodiesterase signaling to quiet nasal tuft cell calcium responses

Background: Airway tuft cells, also called solitary chemosensory cells, are enriched in nasal polyps and are likely the main epithelial source of interleukin-25 (IL-25) in chronic rhinosinusitis with nasal polyps (CRSwNP). Tuft cells are activated through G protein-coupled receptors (GPCRs) that signal through Ca2+. These receptors may also lower cyclic AMP (cAMP), but whether the cAMP pathway can be used to suppress tuft cell responses is unknown. Methods: Ca2+ and cAMP were measured by live cell imaging in isolated Trpm5-GFP mouse nasal tuft cells, and Ca2+ responses were measured in primary human nasal epithelial air-liquid interface (ALI) cultures from patients with CRSwNP. Defensin and IL-25 release were measured by ELISA and ciliary beat frequency (CBF) by high-speed imaging. Phosphodiesterase (PDE) expression was assessed using publicly available single cell RNA sequencing datasets. Results: Agonists of bitter taste receptors (T2Rs), the succinate receptor SUCNR1, and the A1 adenosine receptor increased Ca2+ in GFP-positive mouse nasal tuft cells. T2R and A1 receptor stimulation also lowered cAMP, and these decreases were blocked by pertussis toxin. Glucose, which activates taste family 1 receptors, increased cAMP. Tuft cells were enriched for Pde2a. PDE2A-selective inhibitors (PF-05180999 and BAY 60-7550) increased cAMP and reduced agonist-evoked Ca2+ responses in mouse tuft cells. In human nasal ALIs, both compounds reduced denatonium-evoked Ca2+ responses, defensin release, and IL-25 release without increasing CBF. Conclusions: GPCRs that activate nasal tuft cells also lower cAMP, and by raising cAMP through PDE2A inhibition, tuft cell Ca2+ signaling and IL-25 release were reduced in vitro.

physiology↗

bioRxiv2026

TAS2R10 Suppresses ABCG2 Transporter-Associated Chemoresistance and Enhances Cisplatin Sensitivity in Head and Neck Squamous Cell Carcinoma

Cisplatin resistance remains a major barrier in head and neck squamous cell carcinoma (HNSCC) treatment. ATP-binding cassette (ABC) transporters contribute to chemoresistance by limiting intracellular drug accumulation. Bitter taste receptor 10 (T2R10) has been implicated in ABC transporter regulation, but its role in HNSCC remains undefined. HNSCC cell lines were treated with T2R10-agonist caffeine (100 or 200 M), cisplatin, or a combination, and viability was assessed by crystal violet assay. T2R10 promoter activity and expression following caffeine exposure were evaluated using a promoter-driven mCherry reporter and RT-qPCR. ABC transporter expression was measured after caffeine treatment and T2R10 gene (TAS2R10) knockdown or overexpression. Associations between tumor TAS2R10 expression and survival were assessed using TCGA data through GEPIA2. Caffeine enhanced the cisplatin-associated reduction in viability in a cell line- and concentration-dependent manner, with the strongest effect seen in UM-SCC47. A significant effect was observed in FaDu at 200 M of caffeine, and minimal response in RPMI 2650. RPMI 2650 cells and FaDu cells exhibited lower baseline TAS2R10 expression and RPMI 2650 cells did not demonstrate enhanced cisplatin sensitivity following caffeine treatment. Caffeine treatment increased TAS2R10 promoter activity and expression and was associated with decreased ABCG2 expression. TAS2R10 knockdown increased ABCG2 and ABCF1 expression, whereas TAS2R10 overexpression reduced ABCG2 and ABCC1 expression. High tumor TAS2R10 expression was associated with improved disease-free survival (log-rank p=0.0071; HR=0.61) but not overall survival. Caffeine enhances cisplatin sensitivity in selected HNSCC models. Caffeine exposure is associated with increased TAS2R10 expression and reduced expression of chemoresistance-associated transporters, particularly ABCG2.

cancer biology↗

bioRxiv2026

Therapeutic scheduling of WEE1 inhibition preserves T cell function and promotes immune control of HPV⁺ tumors

Human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV OPC) is driven by viral E6 and E7 oncoproteins, which disrupt G1 checkpoint control and impose selective dependency on WEE1-mediated G2/M regulation. While this vulnerability confers sensitivity to WEE1 inhibition, its immunologic consequences remain poorly defined, and the challenge of eliciting antitumor immunity without compromising immune fitness has limited clinical translation. Here, we show that WEE1 inhibition elicits durable antitumor immunity in immunocompetent models of HPV OPC. Using murine and human preclinical systems, we demonstrate that the WEE1 inhibitor azenosertib (ZN-c3) mediates tumor control through both cell-autonomous cytotoxicity and immune-dependent mechanisms requiring T cells and conventional dendritic cells. Mechanistically, HPV tumor cells are deficient in STING signaling and fail to mount canonical type I interferon responses. Instead, tumor cell-intrinsic cGAS drives immune activation through STING-competent host cells within the tumor microenvironment, revealing a non-cell-autonomous relay that circumvents viral immune evasion. Intermittent WEE1 inhibition preserves T cell fitness while maintaining antitumor efficacy, and mice achieving complete responses develop immunologic memory capable of rejecting tumor rechallenge. These findings establish intermittent WEE1 inhibition as an immune-permissive therapeutic strategy that enables antigen-specific T cell responses in HPV-driven malignancies and provides a mechanistic rationale for combination with immunotherapy.

cancer biology↗

bioRxiv2025

Quercetin as a Bitter Taste Receptor Agonist with Anticancer Effects in Head and Neck Cancer Cells

Background/ObjectivesQuercetin is a bitter compound with demonstrated anticancer effects in preclinical models of head and neck squamous cell carcinoma (HNSCC). In taste transduction, bitter compounds activate bitter taste receptors (T2Rs), a group of G protein-coupled receptors with downstream signaling that includes cytosolic calcium (Ca2+) release. T2Rs are expressed in HNSCC cells, where their activation induces apoptosis in vitro. Increased T2R expression in HNSCC also correlates with improved patient survival. The objective of this study was to investigate the role of quercetin as an anticancer T2R agonist in HNSCC cells in vitro and ex vivo. MethodsQuercetin-mediated Ca2+ responses were assessed using live cell Ca2+ imaging in the presence of the T2R14 antagonist LF1 and G-protein inhibitor YM-254980 (YM) in UM-SCC-47 and FaDu HNSCC cell lines. Cell viability was evaluated using crystal violet assays in cell lines and MTS assays in patient-derived tumor slices. Mitochondrial depolarization was measured with TMRE in the presence and absence of T2R pathway inhibitors. ResultsQuercetin induced a Ca2+ response in HNSCC cells, which was significantly reduced by LF1 and YM. Quercetin also decreased cell viability in vitro and showed a potential decrease in viability in tumor slices but was not statistically significant. Finally, quercetin caused mitochondrial depolarization, which was reduced in the presence of LF1 but not by YM. ConclusionsIn HNSCC cells, quercetin causes a Ca2+ response that is likely mediated by T2R14, decreases viability, and causes mitochondrial depolarization.

cancer biology↗

bioRxiv2025

T2R5 agonist phendione decreases cell viability and induces apoptosis in head and neck squamous cell carcinoma

Bitter taste receptors (T2Rs), a family of G-protein coupled receptors, are emerging as potential therapeutic targets in head and neck squamous cell carcinoma (HNSCC). Phendione, a known T2R5 agonist, has not been previously investigated in HNSCC. Here, we show that phendione activates endogenously expressed T2R5 in HNSCC cells and ex vivo tumor samples, inducing sustained calcium responses, reducing cell viability, and promoting apoptosis through a T2R5-dependent mechanism. Analysis of The Cancer Genome Atlas data revealed that high T2R5 expression in HNSCC tumors correlates with improved long-term disease-specific survival, suggesting a potential tumor-suppressive role for T2R5. These findings highlight T2R5 as a promising therapeutic target in HNSCC and support further investigation of phendione or other T2R5 agonists as potential anti-cancer agents.

cancer biology↗

bioRxiv2025

Protein Phosphatase 2A Subunit B55 Alpha is Required for Angiotensin Type 2 Receptor Elicited Natriuresis

BackgroundAngiotensin type 2 receptor (AT2R) activation promotes natriuresis in renal proximal tubule cells (RPTCs) counteracting sodium retention stimulated by the AT1R. Early signaling events mediating the natriuretic response with AT2R activation in RPTCs are currently unknown. Our previous research suggested protein phosphatase 2A (PP2A) functions downstream of the AT2R. In this study, we investigated the interaction of PP2A regulatory subunit B55 with the AT2R and requirement for B55 in AT2R signaling and natriuresis. Methods and ResultsRats were subjected to renal interstitial (RI) infusion of vehicle or Compound 21 (C21), a non-peptide specific AT2R agonist, and kidney sections were probed for interactions between PP2A subunits and the AT2R using a proximity ligation assay. A dramatic 6-fold increase in AT2R-B55 interaction in apical brush border membranes of RPTCs was observed with C21 stimulation. In vitro binding of purified AT2R and B55 supported a direct interaction between these two proteins. To determine the requirement for B55 in renal AT2R signaling, siRNA targeting B55 was administered to rats in vivo by RI infusion which resulted in a [~]70% decrease in B55 in RPTCs but not distal tubules. In rats with B55 knockdown in RPTCs, natriuresis in response to C21 was abolished. Simultaneously, C21-elicited AT2R redistribution to and sodium transporter Na+/H+ exchanger-3 (NHE3) retrieval from apical brush border membranes was lost, as observed with confocal immunofluorescence microscopy. Consistent with impaired AT2R signaling, B55 knockdown prevented c-Src phosphorylation in response to C21. B55 knockdown also led to a dramatic 4 to 6-fold increase in AT2R co-localization with the lysosomal marker LAMP1, and a 50% reduction in AT2R co-localization with EEA1 and Rab 7, markers for early and late endosomes, respectively. ConclusionsPP2A B55 directly binds to the activated AT2R and is required for AT2R-elicited natriuresis, AT2R signaling and intracellular trafficking in RPTCs.

physiology↗

bioRxiv2024

Pseudomonas aeruginosa metabolite 3-oxo-C12HSL induces apoptosis through T2R14 and the mitochondrial calcium uniporter

Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper aerodigestive tract. HNSCCs have high mortality rates and current treatments can be associated with severe morbidities. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. We previously discovered that bitter taste receptor 14 (T2R14), a GPCR, kills HNSCC cells when activated by bitter agonists. We are now investigating endogenous bitter ligands that exist in HNSCC tumor microenvironment (TME). The TME includes cells, signaling molecules, and microbes that can greatly influence treatment responses and overall prognosis in HNSCC. Pseudomonas aeruginosa is a gram-negative bacterium that colonizes/infects HNSCC patients. 3-oxo-C12SHL is a quorum-sensing N-acyl homoserine lactone (AHL) secreted by P. aeruginosa which is also a bitter compound. 3-oxo-C12HSL induces apoptosis but this has never been linked to T2R activation. We hypothesized that 3-oxo-C12HSL induces apoptosis in HNSCC via T2R14. We show that 3-oxo-C12HSL activates intracellular Ca2+ responses in HNSCC cells. This is inhibited with T2R14 antagonization. 3-oxo-C12HSL may activate additional Ca2+ channels as the Ca2+ dynamics are independent from store-operated calcium entry (SOCE). 3-oxo-C12HSL inhibits cell viability, depolarizes mitochondria, and produces ROS. This induces apoptosis in HNSCC cells. In a comparative screen of quorum-sensing AHLs, 3-oxo-C12HSL was the only AHL that elicited both a Ca2+ response and reduced cell viability. These results suggest that P. aeruginosa may play a significant role in modulating an anti-tumor TME through 3-oxo-C12HSL. Moreover, 3-oxo-C12HSL could be a novel, higher-affinity bitter therapeutic for HNSCC. Further research is warranted to elucidate the mechanisms of other endogenous T2R agonists present in the TME.

physiology↗

bioRxiv2024

Bitter Taste Receptor Agonists Induce Apoptosis in Papillary Thyroid Cancer

BackgroundPapillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with a 20% recurrence rate. Bitter taste receptors (T2Rs) and their genes (TAS2Rs) may regulate survival in solid tumors. This study examined T2R expression and function in PTC cells. MethodsThree PTC cell lines (MDA-T32, MDA-T68, MDA-T85) were analyzed for expression using RT-qPCR and immunofluorescence. Live cell imaging measured calcium responses to six bitter agonists. Viability and apoptosis effects were assessed using crystal violet and caspase 3/7 activation assays. Genome analysis of survival was conducted. ResultsTAS2R14 was consistently highly expressed in all cell lines. Five bitter agonists produced significant calcium responses across all cell lines. All bitter agonists significantly decreased viability and induced apoptosis. Higher TAS2R14 expression correlated with better progression-free survival in patients (p<0.05). ConclusionsT2R activation by bitter agonists induces apoptosis and higher TAS2R expression is associated with survival, suggesting potential therapeutic relevance in thyroid cancer management.

cancer biology↗

bioRxiv2022

Lidocaine Induces Apoptosis in Head and Neck Squamous Cell Carcinoma Cells Through Activation of Bitter Taste Receptor T2R14

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs and their activation can induce apoptosis. Lidocaine is a local anesthetic used in various clinical applications which can also activate bitter taste receptor 14 (T2R14). Lidocaine may have some anti-tumor effects in other cancers, but the mechanism has been mysterious. Here, we found that lidocaine causes intracellular Ca2+ mobilization through activation of T2R14 in HSNCC cells. T2R14 activation with lidocaine depolarizes the mitochondrial membrane, inhibits cell proliferation, and induces apoptosis. Concomitant mitochondrial Ca2+ influx, ROS production causes T2R14-dependent accumulation of poly-ubiquinated proteins, suggesting inhibition of the proteasome as a novel component of T2R14-induced apoptosis. Lidocaine may have therapeutic potential in HNSCC as a topical gel or intratumor injection, warranting future clinical studies. HIGHLIGHTSO_LILidocaine activates bitter taste receptor 14 (T2R14) to increase intracellular Ca2+ and decrease cAMP in head and neck squamous cell carcinoma (HSNCC) cells C_LIO_LILidocaine decreases cell viability and cell proliferation, depolarizes the mitochondrial membrane, and causes production of reactive oxygen species (ROS) C_LIO_LIT2R14 activation with lidocaine induces apoptosis and inhibits the ubiquitin proteasome system (UPS) C_LIO_LILung squamous cell carcinoma (SCC) cells and HNSCC tumor spheroids undergo apoptosis or structural disbandment, respectively, with lidocaine C_LI

cancer biology↗

bioRxiv2022

Taste receptor T1R3 in nasal cilia detects Staphylococcus aureus D-amino acids to enhance apical glucose uptake

Bitter (T2R) and sweet/umami (T1R) taste receptors serve chemosensory roles throughout the body. In airway cilia, T2Rs detect bacterial metabolites to stimulate bactericidal nitric oxide. T1Rs in solitary chemosensory cells detect glucose in airway surface liquid (ASL) and bacterial D-stereoisomer amino acids to regulate antimicrobial peptides. Using differentiated air-liquid interface cultures of primary nasal cells, we show that the T1R3 receptor is also expressed in human and mouse nasal cell cilia. D-amino acids produced at low mM concentrations by Staphylococcus aureus activate T1R3 to decrease ASL glucose and increase apical glucose uptake by increasing GLUT2 and GLUT10 expression through a {beta}-arrestin pathway. Our data suggests that T1R3 localized to cilia functions as an immune detector for D-amino acids to reduce ASL glucose and potentially limit bacterial growth. Given that glucose protected S. aureus against bactericidal NO produced during T2R activation, the reduced ASL glucose with T1R3 activation may also sensitize bacteria to other innate defenses. HIGHLIGHTSO_LINasal motile cilia express the T1R3 subunit of the sweet taste receptor C_LIO_LIS. aureus D-amino acids activate cilia T1R3 to enhance mucosal glucose uptake C_LIO_LIReduced airway surface liquid glucose likely reduces S. aureus growth C_LIO_LIReduced airway glucose also sensitizes S. aureus to epithelial NO production C_LI

physiology↗

bioRxiv2022

Bitter taste receptor-stimulated nitric oxide innate immune responses are reduced by loss of CFTR function in nasal epithelial cells and macrophages

Bitter taste receptors (T2Rs) are G protein-coupled receptors identified on the tongue but expressed all over the body, including in airway cilia and macrophages, where T2Rs serve an immune role. T2R isoforms detect bitter metabolites (quinolones and acyl-homoserine lactones) secreted by gram negative bacteria, including Pseudomonas aeruginosa, a major pathogen in cystic fibrosis (CF). T2R activation by bitter bacterial products triggers calcium-dependent nitric oxide (NO) production. In airway cells, the NO increases mucociliary clearance and has direct antibacterial properties. In macrophages, the same pathway enhances phagocytosis. Because prior studies linked CF with reduced NO, we hypothesized that CF cells may have reduced T2R/NO responses. Using qPCR, immunofluorescence, and live cell imaging of air-liquid interface cultures, we found primary nasal epithelial cells from both CF and non-CF patients exhibited similar T2R expression, localization, and calcium signals. However, CF cells exhibited reduced NO production also observed in immortalized CFBE41o-CF cells and non-CF 16HBE cells CRISPR modified with CF-causing mutations in the CF transmembrane conductance regulator (CFTR). NO was restored by VX-770/VX-809 corrector/potentiator pre-treatment, suggesting reduced NO in CF cells is due to loss of CFTR function. In nasal cells, reduced NO correlated with reduced ciliary and antibacterial responses. In primary human macrophages, inhibition of CFTR reduced NO production and phagocytosis during T2R stimulation. Together, these data suggest an intrinsic deficiency in T2R/NO signaling caused by loss of CFTR function that may contribute to intrinsic susceptibilities of CF patients to P. aeruginosa and other gram-negative bacteria that activate T2Rs.

physiology↗

bioRxiv2021

HSP90 function is required for T2R bitter taste receptor nitric oxide production and innate immune responses in human airway epithelial cells and macrophages

Bitter taste receptors (T2Rs) are G protein-coupled receptors (GPCRs) expressed in various cell types including ciliated airway epithelial cells and macrophages. T2Rs in these two airway innate immune cell types are activated by bitter products, including some secreted by Pseudomonas aeruginosa, leading to Ca2+-dependent activation of endothelial nitric oxide (NO) synthase (eNOS). NO enhances mucociliary clearance and has direct antibacterial effects in ciliated epithelial cells and increases phagocytosis by macrophages. Using biochemistry and live cell imaging, we explored the role of heat shock protein 90 (HSP90) in regulating T2R-dependent NO pathways in primary sinonasal epithelial cells, primary monocyte-derived macrophages, and a human bronchiolar cell line (H441). We used immunofluorescence to show that H441 cells express eNOS and certain T2Rs and that the bitterant denatonium benzoate activates NO production in an HSP90-dependent manner in cells grown either as submerged cultures and at air liquid interface. In primary sinonasal epithelial cells, we determined that HSP-90 inhibition reduces T2R-stimulated NO production and ciliary beating which are crucial for pathogen clearance. In primary monocyte-derived macrophages, we found that HSP-90 is integral to T2R-stimulated NO production and phagocytosis of FITC-labeled Escherichia coli and pHrodo-Staphylococcus aureus. Our study demonstrates that HSP90 serves an innate immune role by regulating NO production downstream of T2R signaling by augmenting eNOS activation without impairing upstream calcium signaling. These findings suggest that HSP90 plays an important role in airway antibacterial innate immunity and may be an important target in airway diseases like chronic rhinosinusitis, asthma, or cystic fibrosis.

physiology↗

bioRxiv2021

The bitter end: T2R bitter receptor agonists elevate nuclear calcium and induce apoptosis in non-ciliated airway epithelial cells

Bitter taste receptors (T2Rs) localize to airway motile cilia and initiate innate immune responses in retaliation to bacterial quorum sensing molecules (acyl-homoserine lactones and quinolones). Activation of T2Rs leads to calcium-driven NO production that increases cilia beating and directly kills bacteria. Several airway diseases, including chronic rhinosinusitis, COPD, and cystic fibrosis, are characterized by epithelial remodeling, including loss of motile cilia and/or squamous metaplasia. To understand the function of T2Rs within the altered landscape of airway disease, we studied T2Rs in non-ciliated airway cell lines and primary cells de-differentiated to a squamous phenotype. In differentiated cells, T2Rs localize to cilia, however in de-differentiated, non-ciliated cells they localize to the nucleus. Cilia and nuclear import utilize many shared proteins, thus in the absence of motile cilia some T2Rs may target to the nucleus. T2R agonists selectively elevated both nuclear and mitochondrial calcium through a G-protein-coupled receptor, phospholipase C, and InsP3 receptor-dependent mechanism. Additionally, T2R agonists decreased nuclear cAMP, increased nitric oxide, and increased cGMP, consistent with T2R signaling. Furthermore, exposure to T2R agonists led to nuclear calcium-induced mitochondrial depolarization and caspase activation. T2R agonists induced apoptosis in primary bronchial and nasal cells differentiated at air-liquid interface but then induced to a squamous phenotype by apical submersion. Air-exposed well-differentiated cells did not die. This T2R-induced apoptosis may be a last-resort defense against infection, possibly when bacteria have breached the epithelial barrier and reach non-ciliated cells below. However, it may also increase susceptibility of de-differentiated or remodeled epithelia to damage by bacterial metabolites. Moreover, the T2R-activated apoptosis pathway occurs in airway cancer cells. T2Rs may thus contribute to microbiome-tumor cell crosstalk in airway cancers. T2R agonists may also be useful topical therapeutics (e.g., delivered by nasal rinse or nebulizer) for activating airway cancer cell apoptosis without killing surrounding differentiated tissue.

physiology↗

bioRxiv2021

T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma

Better management of head and neck squamous cell carcinomas (HNSCCs) requires a clearer understanding of tumor biology and disease risk. Bitter taste receptors (T2Rs) have been studied in several cancers, including thyroid, salivary, and GI, but their role in HNSCC has not been explored. We found that HNSCC patient samples and cell lines expressed functional T2Rs on both the cell and nuclear membranes. Bitter compounds, including bacterial metabolites, activated T2R-mediated nuclear Ca2+ responses leading to mitochondrial depolarization, caspase activation and ultimately apoptosis. Buffering nuclear Ca2+ elevation blocked caspase activation. Furthermore, increased expression of T2Rs in HNSCCs from The Cancer Genome Atlas (TCGA) is associated with improved overall survival. This work suggests that T2Rs are potential biomarkers to predict outcomes and guide treatment selection, may be leveraged as therapeutic targets to stimulate tumor apoptosis, and may mediate tumor-microbiome crosstalk in HNSCC.

cancer biology↗

bioRxiv2020

Altered polarization of PAR-2 signaling during airway epithelial remodeling

BackgroundProtease-activated receptor 2 (PAR-2) is activated by proteases involved in allergy and triggers airway epithelial secretion and inflammation. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells. ObjectiveWe tested if epithelial remodeling during diseases characterized by loss of cilia and squamous metaplasia may alter PAR-2 polarization. MethodsEndogenous PAR-2 responses were measured by live cell calcium and cilia imaging, measurement of fluid secretion, and quantification of cytokines. We utilized airway squamous cell lines, primary differentiated air-liquid interface cultures, and tissue explants. Cells were exposed to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency. We used concentrations and exposure times that altered epithelial morphology without causing breakdown of the epithelial barrier, likely reflecting early disease states. ResultsPAR-2 signaling in airway squamous cells activated calcium and inflammatory responses. Squamous cells cultured at air liquid interface (ALI) responded to PAR-2 agonists applied both apically and basolaterally. Primary well-differentiated nasal epithelial ALI cultures responded only to basolateral PAR-2 stimulation. Primary cultures exposed to IL-13, cigarette smoke condensate, or reduced retinoic acid responded to both apical and basolateral PAR-2 stimulation. Nasal polyp tissue, but not control middle turbinate, exhibited apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyp and turbinate maintained basolateral PAR-2 polarization. ConclusionsSquamous metaplasia and/or loss of cilia enhances apical PAR-2 responses. Altered PAR-2 polarization in dedifferentiated or remodeled epithelia may contribute to increased sensitivity to inhaled protease allergens in inflammatory airway diseases.

physiology↗