IL-17A mediates pyroptosis via the ERK pathway and contributes to steroid resistance in CRSwNP.

BACKGROUND: Pyroptosis is closely related to inflammation. However, the molecular mechanisms and pathologic contributions of pyroptotic epithelial cell are not yet fully understood. OBJECTIVE: This study aimed to explore the function and molecular mechanisms of IL-17A on human nasal epithelial cell (hNEC) pyroptosis. METHODS: The expression of pyroptosis-related biomarkers and IL-17A was assessed in sinonasal mucosa from control individuals, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by using quantitative RT-PCR. Their localization was analyzed via immunohistochemistry and immunofluorescence. The ultrastructural characteristics of IL-17A-induced pyroptosis in hNECs were visualized by using electron microscopy. IL-17A functional assays were performed on hNECs and airway epithelial cell lines. Cytokine levels were quantified via ELISA. The signaling pathways involved in IL-17A-induced pyroptosis were studied via unbiased RNA sequencing and Western blotting. RESULTS: The expression of IL-17A and the pyroptotic biomarkers NOD-like receptor family, pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D, and IL-1ß was increased in nasal mucosa from patients with CRSwNP compared with in those with chronic rhinosinusitis without nasal polyps and the control subjects. IL-17A was positively correlated and colocalized with the pyroptotic biomarkers. IL-17A treatment induced pyroptosis in the hNECs and cell lines analyzed, primarily through the extracellular signal-regulated kinase (ERK)-NLRP3/caspase-1 signaling pathway, and increased IL-1ß and IL-18 secretion in hNECs. Moreover, IL-17A-induced pyroptosis contributed to steroid resistance by affecting glucocorticoid receptor-α and glucocorticoid receptor-ß expression, and the inhibition of pyroptotic proteins partially abolished IL-17A-induced steroid resistance in hNECs. CONCLUSION: Elevated IL-17A level promotes pyroptosis in hNECs through the ERK-NLRP3/caspase-1 signaling pathway and contributes to glucocorticoid resistance by affecting glucocorticoid receptor homeostasis in patients with CRSwNP.

Budesonide nasal irrigation improved Lund-Kennedy endoscopic score of chronic rhinosinusitis patients after endoscopic sinus surgery.

PURPOSE: Budesonide improves the prognosis of chronic rhinosinusitis (CRS). However, few reports have examined whether its use for nasal irrigation, compared to normal saline, improves the prognosis of patients after endoscopic sinus surgery (ESS). We compared the effects of nasal irrigation with budesonide and normal saline in CRS patients after ESS. METHODS: Sixty CRS patients who had undergone ESS were randomly divided into an experimental group (30 patients), which used budesonide nasal irrigation, and a control group (30 patients), which used normal saline nasal irrigation. All patients received regular follow-up evaluations and were assessed via questionnaires, including the Lund-Kennedy endoscopic score (LKES), the symptom visual analog scale (VAS), the 22-item Sino-Nasal Outcome Test (SNOT-22), the Short-Form 36-Item Questionnaire (SF-36), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS) and a side effects scale. RESULTS: Scores of polyposis, mucosal edema, secretions and total score of LKES; VAS scores of nasal blockage, hyposmia and rhinorrhea; and SNOT-22 results in both groups were significantly improved 3 months after ESS. Scores of polyposis, mucosal edema, secretions and scarring and total score of LKES in experimental group were significantly better than in control group 3 months after ESS. No significant differences were observed in SF-36, SAS or SDS before or 3 months after ESS within or between the two groups. The side effects of the two groups were not significantly different. CONCLUSIONS: Nasal irrigation improved the prognosis of CRS patients after ESS. Budesonide nasal irrigation had a better effect than normal saline nasal irrigation.

Vγ1⁺ γδT Cells Are Correlated With Increasing Expression of Eosinophil Cationic Protein and Metalloproteinase-7 in Chronic Rhinosinusitis With Nasal Polyps Inducing the Formation of Edema.

PURPOSE: We have found that expression of γδT cells is increased in pathological mucosa of chronic rhinosinusitis with nasal polyps (CRSwNP) compared with normal nasal mucosa. This increase is correlated with the infiltration of eosinophils in CRSwNP. Here, we investigated the expression of γδT cells, inflammation and tissue remodeling factors as well as their probable relationships in different types of chronic rhinosinusitis (CRS) in China. METHODS: A total of 76 surgical tissue samples that included 43 CRSwNP samples (15 eosinophilic and 28 non-eosinophilic), 17 CRS samples without nasal polyps (CRSsNP), and 16 controls were obtained. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression levels of Vγ1⁺ γδT cells, Vγ4⁺ γδT cells, eosinophil cationic protein (ECP), interleukin (IL)-8, transforming growth factor (TGF)-ß2, metalloproteinase (MMP)-7, tissue inhibitor of metalloproteinase (TIMP)-4 and hypoxia-inducible factor (HIF)-1α. Enzyme linked immunosorbent assay (ELISA) was used to measure the protein level of ECP and MMP-7 in CRSwNP. The eosinophils were counted and the level of edema was analyzed with HE staining. RESULTS: The mRNA expression levels of the Vγ1 subset, ECP and MMP-7 were significantly increased in CRSwNP with histological characteristics of eosinophilic infiltration and edema. The expression of the Vγ1 gene in CRSwNP correlated positively with the expression of both ECP and MMP-7. No significant decreases in the mRNA expression levels of TGF-ß2, TIMP-4 or HIF-1α were observed in the CRSwNP samples. The expression levels of Vγ1 gene, ECP and MMP-7 were significantly increased in eosinophilic CRSwNP compared to non-eosinophilic CRSwNP. CONCLUSIONS: Our results suggest the associations between Vγ1⁺ γδT cells, ECP and MMP-7 in CRSwNP, indicating that Vγ1⁺ γδT cells can induce the eosinophilic inflammation, which has a further effect on the formation of edema.

[Clinical research on the quality of life in patients with allergic rhinitis].

OBJECTIVE: To explore the quality of life (QOL) outcome in patients with allergic rhinitis (AR). METHODS: A prospective trial was conducted to survey the QOL status of 101 AR patients, in contrast to that of 121 healthy individuals and 97 chronic pharyngitis (CP) patients by generic questionnaire medical outcomes study short-form 36-items health survey (SF-36), and to survey the most troublesome problems of AR patients by disease-specific questionnaire rhinoconjunctivitis quality of life questionnaire (RQLQ). The correlation between SF-36 and RQLQ had also been analyzed. All the results were analyzed statistically. RESULTS: By the assessment of SF-36, the scores of 3 domains (x ± s, the same as follow, the scores were 78.02 ± 18.37, 56.13 ± 17.49, 78.81 ± 16.47, respectively) of AR patients were less than those (84.00 ± 18.36, 74.69 ± 14.13, 83.78 ± 14.31) of healthy individuals (P < 0.05), and the scores of 7 domains (the scores were: 91.78 ± 11.78, 79.16 ± 30.23, 78.02 ± 18.37, 56.13 ± 17.49, 78.81 ± 16.47, 67.66 ± 39.57, 68.78 ± 13.65, respectively) of AR patients were similar with those (94.12 ± 6.88, 80.67 ± 32.38, 73.57 ± 17.96, 59.73 ± 16.58, 80.41 ± 17.01, 63.58 ± 39.99, 66.43 ± 13.71) of CP patients (P > 0.05). By the assessment of RQLQ, in AR patients, both the nasal symptoms and the practical problems got the highest scores (the scores were 2.70 ± 1.29, 2.53 ± 1.37 respectively). According to the assessment of the correlation between SF-36 and RQLQ, the correlation was weak (r = -0.199 ∼ -0.526, P < 0.05). CONCLUSIONS: The QOL of AR patients decreased compared with that of healthy individuals, but similar with that of CP patients. The most troublesome problems in AR patients were nasal symptoms and the practical problems. Both SF-36 and RQLQ were suitable for assessing the health status of AR patients. SF-36 and RQLQ each covered a different part of the QOL of AR patients, and the combination of the two questionnaires could improve the QOL measurement.