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Objective Transglutaminase (TGM)2 and peroxisome proliferator-activated receptor (PPAR)γ are thought to participate in the pathogenesis of nasal polyp formation in cystic fibrosis (CF). We herein investigated expressions of cystic fibrosis transmembrane conductance regulator (CFTR), TGM2, PPARγ and isopeptide bonds, a reaction product of TGM, in non-CF nasal polyps. Methods Nasal polyps and inferior turbinates were collected from chronic rhinosinusitis patients without CF during transnasal endoscopic sinonasal surgery. Expressions of CFTR, TGM2, isopeptide bonds and PPARγ were examined by fluorescence immunohistochemistry and quantitative RT-PCR. Expression of CFTR was also analyzed by Western blot. Results Immunohistochemical fluorescence of the nasal polyp was significantly lower for CFTR and PPARγ, and significantly higher for TGM2 and isopeptide bonds than that of the turbinate mucosa. Lower expression of CFTR in the nasal polyp than in the turbinate mucosa was also observed in Western blot. Expression of PPARG mRNA was significantly lower in the nasal polyp than in the turbinate mucosa, whereas expressions of CFTR mRNA or TGM2 mRNA did not differ between the two tissues. Immunohistochemical fluorescence for CFTR showed significant negative correlation with that for TGM2 and isopeptide bonds, and significant positive correlation with that for PPARγ. The fluorescence for TGM2 was positively correlated with that for isopeptide bonds and negatively correlated with that for PPARγ. The fluorescence for isopeptide bonds tended to be negatively correlated with that for PPARγ. Conclusions These results suggest a possible role of the CFTR-TGM2-PPARγ cascade in the pathogenesis of nasal polyp formation in non-CF patients as in CF patients.

Background Mucociliary transport function in the airway mucosa is essential for maintaining a clean mucosal surface. This function is impaired in upper and lower airway diseases. Nasal polyps are a typical pathological feature of prolonged rhinosinusitis. Like the ordinary nasal mucosa, nasal polyps have a ciliated pseudostratified epithelium with vigorous ciliary beating. We herein measured ex vivo mucociliary transport velocity (MCTV) and ciliary beat frequency (CBF) and explored the expressions of planar cell polarity (PCP) proteins in nasal polyps in comparison with turbinate mucosae. Methods Inferior turbinates and nasal polyps were collected from patients with chronic rhinosinusitis during endoscopic sinonasal surgery. Ex vivo MCTV and CBF were measured using a high-speed digital imaging system. Expressions of PCP proteins were explored by fluorescence immunohistochemistry and quantitative RT-PCR. Results The MCTV of nasal polyps was significantly lower than that of the turbinates (7.43±2.01 vs. 14.56±2.09μm/s; P=0.0361), whereas CBF did not differ between the two tissues. The MCTV vector was pointed to the posteroinferior direction in all turbinates with an average inclination angle of 41.0 degrees. Immunohistochemical expressions of Dishevelled-1, Dishevelled-3, Frizzled3, Frizzled6, Prickle2 and Vangl2 were lower in the nasal polyps than in the turbinates. The expression levels of mRNAs for Dishevelled-1, Dishevelled-3 and Frizzled3 in the nasal polyps were also decreased in comparison with the turbinates. Conclusions These results indicate that ciliary transport in nasal polyps is impaired although vigorous ciliary beating is maintained, and that the impairment may be caused by a decrease in Dishevelled/Frizzled proteins and resultant PCP disarrangement.

Background: Nasal breathing is important for maintaining physiological respiration. However, airflow in the nasal cavity has an inherent cooling effect and may suppress ciliary beating, an essential frontline defense in the airway. Nasal airflow is thought to be perceived by transient receptor potential (TRP) M8, a thermoreceptor for cool temperatures. We herein investigated the effect of the activation of thermosensitive TRPs for cool/cold temperatures on ciliary beating and searched for a compensatory mechanism that maintains ciliary beating against the fall of temperature in the human nasal mucosa. Methods and Results: Inferior turbinates were collected from patients with chronic hypertrophic rhinitis, and ex vivo ciliary beat frequency (CBF) was immediately measured using a high-speed digital video camera attached to a phase-contrast light microscope. The samples were also subjected to fluorescence immunohistochemistry and real-time RT-PCR for TRPA1/TRPM8. CBF was significantly increased by adding either cinnamaldehyde (TRPA1 agonist) or l-menthol (TRPM8 agonist), and this increase was inhibited by pannexin-1 blockers, carbenoxolone and probenecid. Immunohistochemistry detected TRPA1 and TRPM8 on the epithelial surface and in the submucosal nasal glands. Expressions of mRNAs for these receptors were confirmed by real-time RT-PCR. Conclusions: These results indicate the stimulatory effect of the activation of TRPA1/TRPM8 on ciliary beating in the nasal mucosa, which would be advantageous to maintain airway mucosal defense under normal nasal breathing. This stimulatory effect is likely to be mediated by pannexin-1. Understanding the regulatory mechanism of airway ciliary beating should aid in the development of new, effective treatments for intractable airway diseases. BackgroundNasal breathing is important for maintaining physiological respiration. However, airflow in the nasal cavity has an inherent cooling effect and may suppress ciliary beating, an essential frontline defense in the airway. Nasal airflow is thought to be perceived by transient receptor potential (TRP) M8, a thermoreceptor for cool temperatures. We herein investigated the effect of the activation of thermosensitive TRPs for cool/cold temperatures on ciliary beating and searched for a compensatory mechanism that maintains ciliary beating against the fall of temperature in the human nasal mucosa.