Effects and clinical significance of NLRP3 inflammasome activated by IL-17A in CRSwNP / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the effects and clinical significance of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activated by interleukin (IL)-17A in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021 were collected, including 28 CRSwNP (including 19 males and 9 females, aged 19 to 67 years), 22 chronic rhinosinusitis without nasal polyps (CRSsNP) and 22 controls. qRT-PCR was used to detect the expressions of IL-17A, NLRP3, IL-1β and IL-18 in the three groups, and their correlations were analyzed. The positions of IL-17A, NLRP3 and IL-18 in nasal polys were analyzed by immunofluorescence. Western Blotting and ELISA were employed to detect the expression of NLRP3, IL-1β and IL-18 in the human nasal epithelial cells after using IL-17A stimulation or IL-17A receptor inhibitor. Immunofluorescence was used to observe the NLRP3, IL-1β, and IL-18 protein expression after IL-17A stimulating human nasal epithelial cells, and after the use of IL-17A receptor inhibitor and NLRP3 inhibitor MCC950. The correlations between NLRP3, IL-1β, IL-18 and CT scores, nasal endoscopic scores, visual analogue scale (VAS) scores, and sino-nasal outcome test (SNOT) 22 scores of CRSwNP patients were analyzed. SPSS 20.0 software was used for statistical analysis. Results: The expressions of IL-17A, NLRP3, IL-1β and IL-18 in the tissues of CRSwNP patients were significantly higher than those in CRSsNP group(P=0.018,P<0.001,P=0.005, P=0.016) and the control group(all P<0.001). IL-17A was positively correlated with the expression of NLRP3, IL-1β, and IL-18(r ralue was 0.643,0.650,0.629,respectively, all P<0.05). IL-17A, NLRP3, and IL-18 were co-localized in the epithelial propria of polyp tissue. IL-17A stimulated the expressions of NLRP3, IL-1β, and IL-18 in human nasal epithelial cells. After the use of IL-17A receptor inhibitor, the expressions of NLRP3, IL-1β, and IL-18 were significantly down-regulated. After the use of NLRP3 inhibitor MCC950, IL-17A was significantly down-regulated to promote the expression of NLRP3, IL-1β, and IL-18. The expressions of NLRP3, IL-1β and IL-18 were positively correlated with CT, nasal endoscopy, VAS, and SNOT22 scores in patients with CRSwNP. Conclusions: IL-17A promotes the release of IL-1β and IL-18 by activating the NLRP3 inflammasome and aggravates the severity of the disease in CRSwNP.

Increased expression of pendrin in eosinophilic chronic rhinosinusitis with nasal polyps / Expressão aumentada de pendrina na rinossinusite crônica eosinofílica com pólipos

Abstract Introduction: Chronic rhinosinusitis with nasal polyps is a heterogeneous disease and appropriate diagnostic algorithms in individual cases are necessary for effective medical treatment. Objective: The purpose of this study was to clarify the relationship between the pendrin expression of nasal polyps and clinical and pathological characteristic features of eosinophilic chronic rhinosinusitis. Methods: A total of 68 patients were classified into eosinophilic chronic rhinosinusitis or non-eosinophilic chronic rhinosinusitis groups according to the degree of eosinophilic infiltration into the nasal polyps. Clinical, hematological, and immunohistochemical analyses were performed and statistically compared between both groups. Results: Thirty-eight were classified into eosinophilic chronic rhinosinusitis and 30 into non-eosinophilic chronic rhinosinusitis groups. There were no significant differences in age distribution, sex ratio, prevalence of asthma, or any other complications between the groups. The mean Lund-Mackay score and the number of serum eosinophils was significantly higher in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. The pendrin expression was more frequently detected in the epithelial surface layer of nasal polyps in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. In addition, mucin 5AC was more widely expressed in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis. Conclusion: Increased expression of pendrin and mucin 5AC in the nasal polyps would be associated with development of eosinophilic chronic rhinosinusitis. This finding could allow the development of a novel therapeutic agent targeted specifically to patients with eosinophilic chronic rhinosinusitis.

Resumo Introdução: A rinossinusite crônica com pólipos nasais é uma doença heterogênea e algoritmos diagnósticos apropriados em casos individuais são necessários para um tratamento médico eficaz. Objetivo: O objetivo deste estudo foi esclarecer a relação entre a expressão da pendrina de pólipos nasais e propriedades clínicas e patológicas características da rinossinusite crônica eosinofílica. Método: Um total de 68 pacientes foram classificados como tendo rinossinusite crônica eosinofílica ou rinossinusite crônica não eosinofílica de acordo com o grau de infiltração eosinofílica nos pólipos nasais. Análises clínicas, hematológicas e imunohistoquímicas foram realizadas e comparadas estatisticamente entre os dois grupos. Resultados: Entre os pacientes, 38 apresentavam rinossinusite crônica eosinofílica e constituíram o grupo 1; 30 tinham rinossinusite crônica não eosinofílica e constituíram o grupo 2. Não houve diferenças significantes na distribuição etária, razão entre os sexos, prevalência de asma ou qualquer outra complicação entre os grupos. O escore médio de Lund-Mackay e o número de eosinófilos séricos foram significantemente maiores no grupo com rinossinusite crônica eosinofílica do que no grupo com rinossinusite crônica não eosinofílica. A expressão da pendrina foi mais frequentemente detectada na camada epitelial superficial dos pólipos nasais na rinossinusite crônica eosinofílica do que no grupo com rinossinusite crônica não eosinofílica. Além disso, mucina 5AC foi mais amplamente expressa na rinossinusite crônica eosinofílica do que na rinossinusite crônica não eosinofílica. Conclusão: O aumento da expressão da pendrina e mucina 5AC nos pólipos nasais estaria associado ao desenvolvimento de rinossinusite crônica eosinofílica. Esse achado pode permitir o desenvolvimento de um novo agente terapêutico voltado especificamente para pacientes com rinossinusite crônica eosinofílica.

Expression of RANTES, eotaxin-2, ICAM-1, LFA-1 and CCR-3 in chronic rhinosinusitis patients with nasal polyposis / Expressão de RANTES, eotaxina-2, ICAM-1, LFA-1 e CCR-3 em pacientes com rinossinusite crônica associada à polipose nasossinusal

PURPOSE: To compare gene expression of the chemokines RANTES and eotaxin-2, its receptor, CCR-3, adhesion molecule ICAM-1 and its receptor LFA-1 in eosinophilic polyps and in control normal nasal mucosa. METHODS: Gene expression was quantified by Real Time PCR in polyps (n=35) and in healthy nasal mucosa (n=15). RESULTS: Eosinophilic polyps showed a higher expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa. CONCLUSION: Eosinophilic polyps present greater expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa.

OBJETIVO: Comparar a expressão gênica das quimiocinas RANTES e eotaxina-2, do seu receptor CCR-3, da molécula de adesão ICAM-1 e do seu receptor LFA-1 entre pólipos nasais eosinofílicos (PE) (n=35) e mucosa nasal controle (n=15). MÉTODOS: Quantificou-se a expressão gênica dos mediadores citados pela técnica de PCR em tempo real em PEs e em mucosas de concha média de pacientes sem doenças nasais ou alteração endoscópica. RESULTADOS: Pólipos eosinofílicos apresentam maior expressão de eotaxina-2 e RANTES, mas não de CCR-3, ICAM-1 e LFA-1, quando comparados as mucosas nasais controles. CONCLUSÃO: Pólipos eosinofícios apresentaram maior expressão de eotaxin-2 and RANTES, mas não de CCR-3, ICAM-1 ou LFA-1,comparada à mucosa nasal controle.

Inmunohistochemical evaluation of estrogen receptors alpha and beta in normal inferior turbinate mucosa / Evaluación inmunohistoquímica de los receptores de estrógenos alfa y beta en la mucosa normal de concha nasal inferior

It has been postulated that the nasal mucosa, like other human tissues, is affected by a complex interactive network of neuropeptides, cytokines, allergic and inflammatory mediators and hormones such as estrogen, in which associations between symptoms (e.g. nasal stuffiness and coryza) and hormonal variations deriving from pregnancy, use of hormonal contraceptives and menstrual cycle phases are observed. The objective is evaluating the presence of specific estrogen receptors (types alpha and beta) in inferior turbinate mucosa in healthy subjects without nasal symptoms. Samples of nasal inferior turbinate were removed from patients undergoing aesthetic nasal surgery, and analyzed using hematoxylin-eosin staining, followed by immunohistochemical preparations on paraffin-embedded sections from the material sample, to detect estrogen receptors alpha and beta. Positive immunohistochemical reactions for both beta and alpha receptors were found in various regions of the inferior nasal turbinate. In conclusion both alpha and beta receptors were found, though the expression of beta was greater and more intense in the anterior portion of the inferior turbinate. No difference was found between male and female patients regarding the intensity of expression of receptors in the inferior turbinate.

Se ha postulado que la mucosa nasal, al igual que otros tejidos humanos, se ve afectada por una compleja red interactiva de neuropéptidos, citoquinas, mediadores alérgicos e inflamatorios, y hormonas como el estrógeno, en el que las asociaciones entre los síntomas (por ejemplo, congestión nasal y catarro) y hormonales las variaciones derivadas del embarazo, se observó el uso de anticonceptivos hormonales y las fases del ciclo menstrual. El objetivo es evaluar la presencia de receptores de estrógenos específicos (tipos de alfa y beta) en la mucosa de la concha nasal inferior en sujetos sanos sin síntomas nasales. Las muestras de la concha nasal inferior fueron retirados de los pacientes sometidos a cirugía nasal estética y analizados mediante hematoxilina-eosina, seguidos de cortes de preparados de inmunohistoquímica incluídos en parafina de la muestra de material, para detectar los receptores de estrógenos alfa y beta. Las reacciones de inmunohistoquímica fueron positiva para ambos receptores alfa y beta, éstas se encuentran en diversas regiones del cornete nasal inferior. En conclusión, tanto los receptores alfa y beta se encuentran, aunque la expresión de la beta fue mayor y más intensa en la porción anterior de la concha nasal inferior. No se encontraron diferencias entre pacientes hombres y mujeres en relación con la intensidad de la expresión de los receptores en el concha nasal inferior.

Evaluation of serum vitamin a levels in patients with Rhinitis

The aim of this study is to evaluate serum vitamin A levels in patients with rhinitis. A case control study concerned with 48 patients with rhinitis who underwent serum vitamin A evaluation and compared with the corresponding results of 100 apparently healthy persons as a control group. The study was carried out in Department of ENT in Al-Salam Teaching Hospital in Mosul, from April 2001 to June 2004. Vitamin A evaluation was performed in Department of Biochemistry in Mosul Medical College. The parameters analyzed included age, sex, clinical diagnosis and vitamin A measurement. The average age was 25 years with a range of 3-52 years. It was found that patients with rhinitis had significantly lower serum vitamin A levels than the control subjects. The levels were 0.292 +/- 0.099 [SD] micro mol/liter versus 0.886 +/- 0.199 [SD] micro mol/ liter, respectively. These findings prompted us to suggest a hypothesis that in rhinitis and possibly in other respiratory tract infections, a general derangement in vitamin A handling exists

Expresión de óxido nítrico sintetasa en mucosa sinusal de pacientes portadores de sinusitis crónica versus controles / Expression of nitric oxide synthase in sinus mucosa of chronic sinusitis patients vs controls

Introducción: El óxido nítrico producido en las cavidades paranasales juega un importante rol en la fisiología nasal ya que aumenta la frecuencia del batido ciliar, optimiza el barrido mucociliary tiene un efecto bacteriostático y virustático. Diversos estudios muestran que el óxido nítrico nasal exhalado en pacientes con rinosinusitis crónica es significativamente más bajo que en sujetos sanos. Esto podría estar determinado por una alteración en la difusión del óxido nítrico a través de los ostia de drenaje obstruidos o por una menor producción de óxido nítrico por parte de los portadores de rinosinusitis crónica. En este último caso, esto podría corresponder al evento primario en la etiopatogenia de la rinosinusitis crónica. Objetivos: Estudiar y comparar cualitativamente con técnica de inmunohisto-química la expresión de las isoformas e-NOS e I-NOS de la óxido nítrico sintetasa en mucosa sinusal de pacientes con rinosinusitis crónica y pacientes controles, sin patología rinosinusal infecciosa o alérgica. Material y método: Para responder a esta interrogante se realizó un estudio comparativo de casos y controles, con el objetivo de cuantificar con técnica de inmunohistoquímica la expresión de las isoformas endotelial e inducible de la óxido nítrico sintetasa en mucosa sinusal de pacientes con rinosinusitis crónica y pacientes controles sin patología rinosinusal infecciosa o alérgica. Resultados: Ingresan al estudio un total de 11 pacientes. Seis de ellos son el grupo control y 5 con sinusitis crónica. Ambos grupos presentan resultados similares. Conclusión: Los resultados no muestran ninguna diferencia en la expresión de óxido nítrico sintetasa, tanto en su isoforma endotelial como inducible, en la mucosa sinusal de pacientes portadores de rinosinusitis crónica comparado con sujetos sanos.

Introduction. Nitric oxide produced in the paranasal sinuses plays an important role in nasal physiology because it increases ciliary beat frequency, improves mucociliary clearance and has a bacteriostatic and virustatic effect. Several studies have shown that exhaled nasal nitric oxide was substantially lower in chronic sinusitis patients, compared to healthy subjects. This could be determined by altered nitric oxide diffusion through obstructed drainage ostia, or by chronic sinusitis patients having lower nitric oxide production. Aims. To qualitatively compare by immunocytochemistry the expression of the iNOS and eNOS isoforms of nitric oxide synthase in the sinus mucosa of chronic sinusitis patients and control subjects. Materials and methods. A case-control comparative study was carried out in order to compare by immunocytochemistry the expression of inducible and epithelial isoforms of nitric oxide synthase in nasal mucosa of chronic sinusitis patients and control subjects, with no infectious or allergic rhinosinusal pathology. Results. The results show no difference in the expression of the inducible or epithelial isoform of nitric oxide synthase in the nasal mucosa of chronic sinusitis patients as compared to healthy subjects.

Eosinophil Inflammation of Nasal Polyp Tissue: Relationships with Matrix Metalloproteinases, Tissue Inhibitor of Metalloproteinase-1, and Transforming Growth Factor-beta1

Eosinophil and mast cell infiltrations are consistent findings in nasal polyp tissue. Previous studies have shown that matrix metalloproteinases (MMPs) may be involved in eosinophil infiltration in airway mucosa of asthmatic patients, and that transforming growth factor-beta1 (TGF-beta1) induces extracellular matrix deposition in nasal polyp tissue. The aim of this study was to evaluate the role of MMPs and tissue-inhibitor of metalloproteinase-1 (TIMP-1) in association with TGF-beta1, eosinophils and mast cell activation in nasal polyp tissue. Nasal polyp tissues from 20 patients who underwent polypectomies were collected and prepared into tissue homogenate. Eosinophil cationic protein (ECP) and tryptase levels were measured by CAP system (Pharmacia, Sweden). MMP-2, MMP-9, TIMP-1 and TGF-beta1 levels were measured by enzyme-liked immunosorbent assay. MMP-2 was the predominant form of MMPs, followed by MMP-9 and TIMP-1. There were significant correlations between ECP, and MMP-9, MMP-2, TGF-beta1 and tryptase, but not with TIMP-1. Significant correlations were noted between tryptase, and MMP-2, MMP-9, and TGF-beta1, but not with TIMP-1. Close correlations were noted between TGF-beta1, and MMP-9 and MMP-2, but not with TIMP-1. MMP-2, MMP-9, and TGF-beta1 may contribute to eosinophil and mast cell migrations into nasal polyp tissue.