Aquaporin expression profiles in normal sinonasal mucosa and chronic rhinosinusitis.

Thickened secretions, mucosal edema, and polyp formation are pathological features in chronic rhinosinusitis (CRS) that could theoretically be caused by aberrant water flow through sinonasal mucosa. Aquaporins (AQPs) are a family of proteins with roles in water transport, with tissue-specific expression profiles. This study aims to determine if AQP expression in sinonasal mucosa is different between normal controls and patients with CRS, either with (CRSwNP) or without (CRSsNP) nasal polyps. During endoscopic sinus surgery or transsphenoidal surgery, sinonasal tissue was collected and classified as CRSwNP (n = 13), CRSsNP (n = 10), or normal (n = 10). Messenger RNA (mRNA) expression of human AQP0 to AQP12b was determined using quantitative real-time polymerase chain reaction (qRT-PCR). Cellular localization of AQP1, AQP3, AQP4, AQP5, AQP7, and AQP11 was determined by immunohistochemistry. mRNA of AQP0 to AQP11 was identified in all samples. AQP12b mRNA was not detected. Significant differences in the mRNA expression levels of AQP4 and AQP11 were identified between normal and CRSwNP patients (p < 0.05). Differences in the cellular localization of AQPs were observed in both CRSsNP and CRSwNP patients vs normal controls. More intense localization to the cell cytoplasm was observed for AQP5 in glandular epithelium (CRSwNP; p < 0.05) and surface epithelium (CRSsNP; p < 0.05), and AQP4 in glandular epithelium (CRSsNP; p < 0.05). This study characterized AQP mRNA expression and protein localization in normal human sinonasal tissue. Significant differences in mRNA expression were found for AQP4 and AQP11 in CRSwNP and differences in protein localization patterns of AQP4 and AQP5 were identified in both types of CRS.

Frauenfelder C ，Woods C ，Hussey D ，Ooi E ，Klebe S ，Carney AS ... -  《-》

Expression and localization of aquaporin 1, 2, 3, 4, and 5 in human nasal mucosa.

Seno S ，Ogawa T ，Shibayama M ，Kouzaki H ，Shimizu T ... -  《-》

Reduced sinonasal levels of 1α-hydroxylase are associated with worse quality of life in chronic rhinosinusitis with nasal polyps.

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have deficiencies in circulating and sinonasal levels of the inactive form of vitamin D3, 25-hydroxycholecalciferol (25VD3). Moreover, CRSwNP patients have reduced epithelial cell-specific expression of 1α-hydroxylase; the enzyme responsible for the conversion of 25VD3 to its metabolically active form, 1α,25-dihydroxyvitamin D3 (1,25VD3). The objective of this work was to determine the impact of sinonasal 1α-hydroxylase levels combined from all cellular sources on subjective disease severity and to identify variables influencing its expression. Blood and sinus tissue explants were collected at the time of surgery from control, chronic rhinosinusitis without nasal polyps (CRSsNP), CRSwNP, and allergic fungal rhinosinusitis (AFRS) patients. 1α-Hydroxylase was measured by immunostaining with flow cytometric analysis. Subjective disease severity was measured by the 22-item Sino-Nasal Outcomes Test (SNOT-22). 1,25VD3 and 25VD3 were measured by enzyme-linked immunosorbent assay (ELISA). Patients with CRSwNP or AFRS have reduced 1α-hydroxylase and 1,25VD3 compared to controls or CRSsNP. Circulating 1,25VD3 levels were the same among all groups. No differences in sinonasal 1α-hydroxylase or 1,25VD3 were found between CRSwNP and AFRS. Gender, age, race, atopy, and systemic 25VD3 had no impact on sinonasal 1α-hydroxylase levels in any group. However, CRSwNP patients with asthma had higher 1α-hydroxylase than those without asthma. Total 1α-hydroxylase levels inversely correlated with SNOT-22 in CRSwNP, but not CRSsNP. Patients with CRSwNP and AFRS both have reduced sinonasal 1α-hydroxylase and 1,25VD3 compared to controls or CRSsNP. Reductions in intracellular 1α-hydroxylase combined from all sinonasal cell types were associated with more severe subjective disease severity in CRSwNP.

Schlosser RJ ，Carroll WW ，Soler ZM ，Pasquini WN ，Mulligan JK ... -  《-》

Nasal interleukin 25 as a novel biomarker for patients with chronic rhinosinusitis with nasal polyps and airway hypersensitiveness: A pilot study.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airway and is tightly linked with airway hyperresponsiveness (AHR) and asthma. However, the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP remain elusive. To investigate the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP. In this study, sinonasal tissues were collected from 42 patients with CRSwNP (asthma, n = 17; asymptomatic AHR, n = 11; non-AHR, n = 14), 11 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 13 controls. The protein and messenger RNA levels of interleukin (IL) 25 and other cytokines in nasal polyp (NP) and control sinonasal tissues were determined by quantitative real-time polymerase chain reaction and multiplex immunoassay, respectively. Multivariate logistic regression and receiver operating characteristic curve analysis were performed to assess the clinical relevance of IL-25. We found that the protein and messenger RNA levels of IL-25 were significantly increased in NP tissues compared with the control sinonasal tissues from patients with CRSwNP, patients with CRSsNP, and controls. Multivariate logistic regression revealed that the nasal IL-25 protein level and nasal and blood eosinophil counts were independent risk factors for AHR in patients with CRSwNP. According to receiver operating characteristic curve analysis, nasal tissue IL-25 had a sensitivity of 91.4% and a specificity of 62.8% (area under the curve, 0.845) at the cutoff level of 5 pg/μL for indicating AHR in this CRSwNP cohort. Our findings indicated that IL-25 was significantly increased in NP tissues and may be considered as the molecular indicator for AHR in patients with CRSwNP. ClinicalTrials.gov Identifier: NCT02110654.

Chen F ，Hong H ，Sun Y ，Hu X ，Zhang J ，Xu G ，Zhao W ，Li H ，Shi J ... -  《-》

Sinonasal epithelial cell expression of toll-like receptor 9 is decreased in chronic rhinosinusitis with polyps.

Ramanathan M Jr ，Lee WK ，Dubin MG ，Lin S ，Spannhake EW ，Lane AP ... -  《-》