1.Compliance and withdraw reason of sublingual immunotherapy in 245 patients with allergic rhinitis.
Caifeng XIA ; Rong YAN ; Quangui WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(4):277-281
		                        		
		                        			
		                        			Objective:To investigate the compliance of patients with allergic rhinitis(AR) receiving sublingual immunotherapy and its influencing factors. Methods:The clinical data of 291 AR patients who received sublingual immunotherapy for dust mites at the First Hospital of Peking University from January 2016 to January 2018 were retrospectively analyzed, and their outpatient or telephone follow-up was conducted. For patients whose treatment time was less than 2 years, the time and reason for the loss were recorded, and the factors affecting their compliance were discussed from the aspects of gender, age, and education. Results:Among the 291 patients, 245 cases(84.2%) were successfully followed up, and 193 cases(78.8%) fell off midway(treatment time<2 years). The overall compliance rate was 21.22%(52/245). The compliance rate of children is higher than that of adults(χ²=21.306, P<0.05), and gender and education level have no significant effect on the compliance rate. The time period for the largest number of shedding was 6-<12 months after treatment(68 cases, 27.8%). The main cause of shedding was symptom relief, which was considered cured(16.7%). Secondly, within 3 months after treatment, a total of 61 patients(24.9%) fell off, of which 34 cases(13.9%) fell off because of troublesome medication, often missed medication, and simply stopped taking the drug. Statistics on the overall reasons for shedding in 193 patients, the top three shedding reasons were: cured after symptom relief(59 cases, 30.6%), troublesome medication, discontinuation after missed dose(44 cases, 22.8%), slow onset or ineffectiveness(26 cases, 13.5%). Conclusion:The overall compliance of sublingual immunotherapy in patients with allergic rhinitis is poor, and the compliance of children is better than that of adults. Clinicians should focus on the reasons for patients to fall off at various times, strengthen patient education, enhance patient confidence in treatment, and improve the compliance of patients.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Sublingual Immunotherapy
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Rhinitis, Allergic/drug therapy*
		                        			;
		                        		
		                        			Desensitization, Immunologic
		                        			;
		                        		
		                        			Pyroglyphidae
		                        			;
		                        		
		                        			Immunotherapy
		                        			;
		                        		
		                        			Antigens, Dermatophagoides/therapeutic use*
		                        			
		                        		
		                        	
2.Evaluation of subjective scale in allergen nasal provocation test.
Li SHEN ; Xiuxiu HU ; Liang ZENG ; Yuanhua LIU ; Ying WU ; Huarong YI ; Qing LUO ; Jing YE
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(6):423-427
		                        		
		                        			
		                        			Objective:To compare the clinical value of visual analogue scale (VAS), Lebel scale and total nasal symptom scores (TNSS) in evaluating nasal allergen provocation test (NAPT). Methods:A total of 151 patients suspected of allergic rhinitis admitted to the Department of Otolaryngology-Head and Neck Surgery of our hospital from April 2020 to September 2020 were included, of which 76 were positive for house dust mites and 75 were negative for allergens. Nasal airway resistance(NAR) was measured by active anterior nasal manometry. Nasal symptoms were evaluated by VAS, Lebel and TNSS. House dust mite allergen was used for NAPT by spray method. An increase≥40% in NAR was used as the gold standard for objective evaluation of NAPT. ROC curves of VAS, Lebel and TNSS were drawn to compare the evaluation effectiveness of different subjective evaluation methods, and the optimal critical point of each ROC curve was obtained. Results:With NAR increased by ≥40% as the gold standard, the area under ROC curve of VAS was 0.884, and the sensitivity and specificity were 97.75% and 80.65%, respectively. The area under ROC curve of Lebel was 0.773, and the sensitivity and specificity were 68.54% and 75.81%, respectively. The area under ROC curve of TNSS was 0.792, and the sensitivity and specificity were 68.54% and 79.03%, respectively. There was no significant difference between Lebel and TNSS(P>0.05). The VAS differed significantly from Lebel and TNSS(P<0.05). The Kappa values of VAS, Lebel, TNSS and NAR were 0.803, 0.432 and 0.459, respectively. Conclusion:The VAS, Lebel, TNSS subjective scale and NAR are consistent in evaluating the efficacy of NAPT, with the VAS assessment showing highest consistency with NAR. As objective assessment instruments are not widely used in China, subjective assessment method could be adopted to evaluate the efficacy of NAPT in clinical practice, and VAS scale is recommended as a priority.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Allergens
		                        			;
		                        		
		                        			Nasal Provocation Tests/methods*
		                        			;
		                        		
		                        			Rhinitis, Allergic/diagnosis*
		                        			;
		                        		
		                        			Nose
		                        			;
		                        		
		                        			Pyroglyphidae
		                        			
		                        		
		                        	
3.Value of allergen nasal provocation test in assessment of the efficacy of house dust mites specific immunotherapy.
Duohui LI ; Hao XIAO ; Shixi LIU ; Qiaoru JIA ; Li ZHANG ; Chuqi SHI ; Juan MENG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(6):428-441
		                        		
		                        			
		                        			Objective:To investigate the value of nasal provocation test(NPT) in evaluating the efficacy of allergen immunotherapy(AIT) in patients with dust mite induced allergic rhinitis(AR). Methods:A total of 83 patients with dust mite induced AR with/without asthma were included. Symptom score(SS), daily medication score(DMS), combined symptom and medication score(CSMS), rhinoconjunctivitis quality of life questionnaire(RQLQ), NPT and skin prick test(SPT) were assessed before and after 1 year AIT. Results:There were statistical differences in SS(P<0.000 1), DMS(P<0.000 1), CSMS(P<0.000 1), and RQLQ(P<0.000 1) after 1 year of AIT compared with pre-treatment. The effective rate of CSMS was 73.49%, and the effective rate of NPT was 42.17%. CSMS was consistent with NPT in efficacy assessment(Kappa=0.437, P<0.001); while in 54 patients with pre-treatment NPT concentrations other than the original concentration, CMSM and NPT showed better consistence(Kappa=0.895, P<0.001). Among the 48 patients with ineffective NPT assessment in the first year, 25 patients completed the second-year follow-up, and 12 patients(48.00%) showed effective in NPT. However, 10 out of 12 patients(83.33%) with NPT concentration other than original solution pre-treatment showed effective NPT at the second year. Conclusion:NPT can be used as one of the indicators for efficacy evaluation for dust mite induced AR patients, especially for patients with positive NPT induced at lower concentrations before treatment.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Pyroglyphidae
		                        			;
		                        		
		                        			Allergens
		                        			;
		                        		
		                        			Nasal Provocation Tests
		                        			;
		                        		
		                        			Quality of Life
		                        			;
		                        		
		                        			Rhinitis, Allergic/therapy*
		                        			;
		                        		
		                        			Desensitization, Immunologic
		                        			;
		                        		
		                        			Skin Tests
		                        			;
		                        		
		                        			Dust
		                        			
		                        		
		                        	
4.Characteristics of allergen component in dust mite-induced allergic rhinitis patients.
Hao CHEN ; Ping JI ; Lin YANG ; Nan HUANG ; Qing JIANG ; Yaqi YANG ; Rongfei ZHU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(6):442-447
		                        		
		                        			
		                        			Objective:To investigate the characteristics of allergen component in dust mite(DM) -induced allergic rhinitis(AR) patients, and provide reference for the diagnosis and treatment of AR. Methods:DM-induced AR patients with or without allergic asthma(AA) who visited the Allergy Department of Tongji Hospital, Huazhong University of Science and Technology between 2021 and 2022 were enrolled. Patients'age, gender, and visual analog scale(VAS) for symptoms were recorded. sIgE and sIgG4 levels of allergen components such as Der f1, Der f2, Der p1, Der p2, Der p7, Der p10, Der p21, and Der p23 were detected using a protein chip method. The sensitization characteristics of the allergen components in the patients were observed, and the correlation between sIgE, sIgG of each component and VAS as well as the component differences between AR and AR with AA(AR&AA) were evaluated. Results:A total of 87 DM-induced AR patients were enrolled, with 42.5% of them were AR&AA, their VAS scores were significantly higher than those of AR patients(6.38±1.95 vs 5.25±1.85, P=0.009 8). The order of sensitization rates for DM components was as follows: Der p2(82.8%), Der f2(81.6%), Der p1(74.7%), Der f1(70.1%), and Der p23(35.6%). The order of positive rates for sIgG4 was: Der p2(21.8%), Der f2(13.8%), Der p21(8.0%), and Der p7(6.9%). There were no correlation between the sIgE, sIgG4 levels or positive numbers of components and VAS scores, but there were positive correlations between sIgE, sIgG4 concentrations of components. Compared with AR patients, AR&AA patients had higher levels of sIgE for Der p(60.5[7.2-91.1]vs 14.0[4.8-45.1], P=0.02), Der f(49.8[15.7-81.6]vs 21.3[7.0-50.2], P=0.04), Der p1(27.2[0.7-51.5]vs 2.6[0.2-24.9], P=0.02), Der p2(20.0[1.4-60.6]vs 5.5[0.6-19.1], P=0.004), and Der f2(58.9[16.0-89.2]vs 23.4[0.9-56.8], P=0.009), and a higher proportion of AR with AA patients had sIgE levels of Der p1(70.3% vs 48.0%, P=0.038) and Der p23(27.0% vs 14.0%, P=0.039) that were ≥3 grades. Conclusion:Der p1/f1, Der p2/f3, and Der p23 are the major components of DM sensitized AR patients. Multiple component sensitization and sIgE, sIgG4 levels of each component are not correlated with the severity of AR. The sIgE levels of the Der p1/f1, Der p2/f3, and Der p23 components in AR&AA patients are higher than AR.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Allergens
		                        			;
		                        		
		                        			Pyridinolcarbamate
		                        			;
		                        		
		                        			Rhinitis, Allergic/therapy*
		                        			;
		                        		
		                        			Pyroglyphidae
		                        			;
		                        		
		                        			Asthma
		                        			;
		                        		
		                        			Antigens, Dermatophagoides
		                        			
		                        		
		                        	
5.Dermatophagoides farinae induces conjunctival epithelial cell damage to promote neutrophil migration and neutrophil extracellular traps formation.
Meili WU ; Ru YAN ; Wenjun ZHAO
Chinese Journal of Schistosomiasis Control 2023;35(3):271-278
		                        		
		                        			OBJECTIVE:
		                        			To investigate the mechanisms underlying allergic conjunctivitis caused by conjunctival epithelial cell damage, neutrophil migration and neutrophil extracellular traps (NETs) formation induced by crude extracts of Dermatophagoides farinae mite (CDM).
		                        		
		                        			METHODS:
		                        			Human conjunctival epithelial cells were stimulated with 500, 1 000, 2 000, 4 000 ng/mL, and the expression levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-8 were detected using quantitative real-time PCR (qPCR) assay and enzyme-linked immunosorbent assay (ELISA). The culture supernatant of human conjunctival epithelial cells was collected and co-cultured with neutrophils. Neutrophil migration was measured using Transwell migration assay, and the expression of NETs markers myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) was quantified using immunofluorescence staining. Neutrophils were stimulated with phorbol 12-myristate 13-acetate (PMA), and then NETs were collected for treatment of human conjunctival epithelial cells. Cell apoptosis was detected using flow cytometry, and the levels of IL-6, TNF-α, IFN-γ and IL-8 were measured in the cell culture supernatant using ELISA.
		                        		
		                        			RESULTS:
		                        			Treatment with CDM at concentrations of 2 000 ng/mL and 4 000 ng/mL up-regulated IL-6, TNF-α, IFN-γ and IL-8 expression in human conjunctival epithelial cells. Following treatment with CDM at concentrations of 2 000 ng/mL and 4 000 ng/mL, the culture supernatant of human conjunctival epithelial cells promoted neutrophil migration and induced increases in the staining intensity of MPO and CitH3. In addition, increased NETs triggered the apoptosis of human conjunctival epithelial cells and IL-6, TNF-α, IFN-γ and IL-8 secretion in the culture supernatant of human conjunctival epithelial cells.
		                        		
		                        			CONCLUSIONS
		                        			CDM induces human conjunctival epithelial cell damages, thereby promoting neutrophil migration and NETs formation, while the release of NETs further aggravates human conjunctival epithelial cell damages.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Extracellular Traps
		                        			;
		                        		
		                        			Neutrophils
		                        			;
		                        		
		                        			Interleukin-8/metabolism*
		                        			;
		                        		
		                        			Dermatophagoides farinae
		                        			;
		                        		
		                        			Interleukin-6/metabolism*
		                        			;
		                        		
		                        			Tumor Necrosis Factor-alpha/metabolism*
		                        			;
		                        		
		                        			Epithelial Cells
		                        			;
		                        		
		                        			Interferon-gamma/metabolism*
		                        			;
		                        		
		                        			Tetradecanoylphorbol Acetate/pharmacology*
		                        			
		                        		
		                        	
6.House dust mite disrupts the airway epithelial barrier by affecting the expression of thymic stromal lymphopoietin through inducing Atg5.
Zicong ZHOU ; Shixiu LIANG ; Zili ZHOU ; Jieyi LIU ; Xiaojing MENG ; Laiyu LIU ; Fei ZOU ; Changhui YU ; Shaoxi CAI
Chinese Medical Journal 2023;136(17):2128-2130
7.Effect of maternal exposure to lipopolysaccharide during pregnancy on allergic asthma in offspring in mice.
Chao Yue MENG ; Xiu Li GONG ; Ran ZHAO ; Quan LU ; Xiao Yan DONG
Chinese Journal of Pediatrics 2022;60(4):302-306
		                        		
		                        			
		                        			Objective: To investigate the effect of maternal exposure to lipopolysaccharide during pregnancy on allergic asthma in offspring in mice. Methods: Animal experimental research was carried out from June 2019 to June 2021.Pregnant C57BL/6J mice were randomly divided into 2 groups by intraperitoneal injection with 7 μg/kg lipopolysaccharide (LPS) or phosphate buffered saline (PBS) at day 15.5 of gestation. After birth, 6 offspring were randomly chosen from each group at the age of 4 weeks, and stimulated with house dust mites (HDM) or PBS, further divided into 4 groups, such as LPS+PBS group, LPS+HDM group, PBS+PBS group, PBS+HDM group, with 3 mice in each group. The cough and wheezing were observed, the histological changes in lung tissue were examined after HE staining, and the expression of inflammatory factors including interleukin (IL)-4, IL-6, IL-17A, IL-23, interferon (IFN)-α and IFN-β in the lung tissue were detected by high-throughput liquid protein chip detection. T test or rank sum test was used for the comparison among these groups. Results: The asthma-like airway inflammation was more obvious in PBS+HDM group after stimulated by HDM than that in PBS+PBS group, nevertheless, this manifestation in LPS+HDM group was milder than that in PBS+HDM group. HE staining showed that inflammatory cell aggregation in the lung tissue in PBS+HDM group was significantly higher than that in PBS+PBS group (4.0 (3.5, 4.0) vs. 0 (0, 0.5), Z=2.02, P=0.043), while it was much lower in LPS+HDM group compared to PBS+HDM group (1.0 (0.5, 1.5) vs. 4.0 (3.5, 4.0), Z=1.99, P=0.046). High-throughput liquid protein chip detection of lung tissue showed that IL-6, IL-23 and IFN-β levels were significantly higher in PBS+HDM group when compared to those in PBS+PBS group ((114±3) vs. (94±4) ng/L, (210±4) vs. (173±7) ng/L, (113±2) vs. (94±4) ng/L, t=4.37, 4.84, 3.96, all P<0.05), while the levels of IL-6, IL-23, IFN-α, IFN-β in LPS+HDM group were significantly lower than those in PBS+HDM group ((87±5) vs. (114±3) ng/L, (171±7) vs. (210±4) ng/L, (16.1±0.6) vs. (20.9±0.3) ng/L, (95±1) vs. (113±2) ng/L, t=5.07, 5.07, 7.28, 7.47, all P<0.05). Conclusions: Prenatal low dose LPS exposure can reduce offspring's airway inflammatory reactions and prevent the development of allergic disease. Maternal infection during pregnancy may affect the occurrence and development of allergic asthma in offspring.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Asthma/etiology*
		                        			;
		                        		
		                        			Disease Models, Animal
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Inflammation
		                        			;
		                        		
		                        			Interleukin-23
		                        			;
		                        		
		                        			Interleukin-6
		                        			;
		                        		
		                        			Lipopolysaccharides
		                        			;
		                        		
		                        			Lung
		                        			;
		                        		
		                        			Maternal Exposure/adverse effects*
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Mice, Inbred C57BL
		                        			;
		                        		
		                        			Pregnancy
		                        			;
		                        		
		                        			Pyroglyphidae
		                        			
		                        		
		                        	
8.Bioinformatics analysis of nasal epithelial cell gene expression in seasonal and perennial allergic rhinitis.
Li Wei SUN ; Zi Yu LIU ; Ji Chao SHA ; Cui Da MENG ; Dong Dong ZHU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(4):425-432
		                        		
		                        			
		                        			Objective: Transcriptome sequencing and bioinformatics analysis were performed on the gene expression of nasal epithelial cells in patients with seasonal allergic rhinitis (AR) and perennial AR, so as to obtain the differences in the gene expression of nasal epithelial cells between seasonal AR and perennial AR. Methods: The human nasal epithelial cell line(HNEpC) was cultured in vitro, treated with 100 μg/ml mugwort or house dust mite (HDM) extracts for 24 hours. Total cell RNA was extracted, and quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression of cytokines, including IL-6, IL-8, IL-33 and thymic stromal lymphopoietin (TSLP). From November 2019 to November 2020, 3 seasonal AR patients, 3 perennial AR patients, and 3 healthy controls who attended the Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University were analyzed. The patients' primary nasal epithelial cells were cultured in vitro, treated with corresponding allergens for 24 hours. Total RNA was extracted for transcriptome sequencing, and the sequencing results were analyzed by bioinformatics. Results: The qPCR results showed that the cytokines IL-6, IL-8, IL-33 and TSLP of HNEpC treated with mugworts extracts and HDM extracts had the same trend of change. After the nasal epithelial cells from patients with seasonal AR and perennial AR were treated with corresponding allergens, there were differences in biological processes and signal pathways between those and control. Gene ontology (GO) enrichment analysis showed that the differentially expressed genes (DEG) in AR patients allergic to mugwort were mainly enriched in the oxidation-reduction process, the negative regulation of apoptosis process, and the cell adhesion; the DEG in AR patients allergic to HDM were mainly enriched in cell adhesion, the negative regulation of cell proliferation and the response to drug. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway showed that the DEG of AR patients allergic to mugwort were significantly enriched in arachidonic acid metabolism, p53 signaling pathway and transforming growth factor β (TGF-β) signaling pathway, while the DEG of AR patients allergic to HDM were mainly enriched in cells cycle, Fanconi anemia pathway and DNA replication. Gene Set Enrichment Analysis (GSEA) showed that the inflammatory response, TNF-α/NF-κB signaling pathway and IL-2/STAT5 signaling pathway were significantly up-regulated in AR patients allergic to mugwort, indicating the promotion of inflammatory response; and AR patients allergic to HDM had significant down-regulation of G2M, E2F, and MYC, indicating the inhibition of cell proliferation. The protein-protein interaction network showed that TNF and CDK1 were the most interacting proteins in mugwort and HDM allergic AR patients, respectively. Conclusion: Seasonal AR and perennial AR may affect the different biological processes and signal pathways of nasal epithelial cells, leading to differences in the occurrence and development of AR.
		                        		
		                        		
		                        		
		                        			Allergens
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Computational Biology
		                        			;
		                        		
		                        			Cytokines/metabolism*
		                        			;
		                        		
		                        			Epithelial Cells/metabolism*
		                        			;
		                        		
		                        			Gene Expression
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Interleukin-33/metabolism*
		                        			;
		                        		
		                        			Interleukin-6/metabolism*
		                        			;
		                        		
		                        			Interleukin-8
		                        			;
		                        		
		                        			Nasal Mucosa/metabolism*
		                        			;
		                        		
		                        			Plant Extracts/metabolism*
		                        			;
		                        		
		                        			Pyroglyphidae
		                        			;
		                        		
		                        			RNA/metabolism*
		                        			;
		                        		
		                        			Rhinitis, Allergic/metabolism*
		                        			;
		                        		
		                        			Rhinitis, Allergic, Perennial
		                        			;
		                        		
		                        			Rhinitis, Allergic, Seasonal
		                        			;
		                        		
		                        			Seasons
		                        			
		                        		
		                        	
9.Analysis of inhaled allergen spectrum characteristics of allergic rhinitis in 5 019 cases in Xinjiang area.
Yan WANG ; Li Mian XIAO ; Hai Su YAN ; Yu Ping YANG ; Ling Ling WANG ; Hua ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(4):474-478
		                        		
		                        			
		                        			Objective: To analyze the characteristics of allergen spectrum in patients with allergic rhinitis (AR) in Xinjiang area in recent 13 years. Methods: The skin prick test (SPT) results of 5 019 AR patients from 2007 to 2019 were retrospectively summarized, and 14 allergens of different age, gender and race were analyzed. Results: The distribution of 14 allergens was significantly different in different years, the difference was significant (P<0.05). The top three positive rates of 14 allergens were quinoa 48.2% (2 398/4 970), plantain 33.3% (1 221/3 667), and Artemisia 33.1% (1 647/4 974). There was no significant difference in the positive rate of dog epithelium between different genders and ages (χ²=0.041, P>0.05; χ²=3.8, P>0.05), the difference of other allergen in positive rates was statistically significant (all P<0.05). The positive rates of Alternaria Alternata (χ²=7.3), Penicillium Sp. (χ²=0.3), Cat Epithelium (χ²=3.1), Dust Mite (χ²=1.4), Acaroid Mite (χ²=0.5) and Cockroach (χ²=2.9) had no significant difference among different races (all P>0.05). The positive rates of other eight allergens including Artemisia Vulgaris (χ²=64.9), Chenopodium (χ²=204.1), Artemisiifolia (χ²=72.4), Plantain (χ²=87.8), Phleum Pratense L(χ²=55.4), Robinia Pseudoacacia (χ²=67.8), Canis Familiari (χ²=70.8), Dog Epithelium (χ²=15.7) were significantly different among different races (all P<0.05). Conclusion: The distribution of allergens in Xinjiang area changes with time, the main allergens are mainly herbaceous, and the distribution of allergens in patients with AR is different in gender, age and race.
		                        		
		                        		
		                        		
		                        			Allergens
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Artemisia
		                        			;
		                        		
		                        			Dogs
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Pyroglyphidae
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Rhinitis, Allergic
		                        			;
		                        		
		                        			Skin Tests
		                        			
		                        		
		                        	
10.HSP90α exacerbates house dust mite-induced asthmatic airway inflammation by upregulating endoplasmic reticulum stress in bronchial epithelial cells.
Hao Hua HUANG ; Yu Jie QIAO ; Yi HUANG ; Hang Ming DONG
Journal of Southern Medical University 2022;42(3):347-353
		                        		
		                        			OBJECTIVE:
		                        			To explore the role of heat shock protein 90α (HSP90α) and endoplasmic reticulum (ER) stress pathway in allergic airway inflammation induced by house dust mite (HDM) in bronchial epithelial cells.
		                        		
		                        			METHODS:
		                        			A HDM- induced asthmatic cell model was established in human bronchial epithelial (HBE) cells by exposure to a concentration gradient (200, 400 and 800 U/mL) of HDM for 24 h. To test the effect of siHSP90α and HSP90 inhibitor 17-AAG on HDM-induced asthmatic inflammation, HBE cells were transfected with siHSP90α (50 nmol, 12 h) or pretreated with 17-AAG (900 nmol, 6 h) prior to HDM exposure (800 U/mL) for 24 h, and the changes in the expression of HSP90α and ER stress markers were assessed. We also tested the effect of nasal drip of 17-AAG, HDM, or their combination on airway inflammation and ER stress in C57BL/6 mice.
		                        		
		                        			RESULTS:
		                        			In HBE cells, HDM exposure significantly up-regulated the expression of HSP90α protein (P=0.011) and ER stress markers XBP-1 (P=0.044), ATF-6α (P=0.030) and GRP-78 (P=0.027). Knocking down HSP90α and treatment with 17-AAG both significantly inhibited HDM-induced upregulation of XBP-1 (P=0.008). In C57BL/6 mice, treatment with 17-AAG obviously improved HDM-induced airway inflammation and significantly reduced the number of inflammatory cells in the airway (P=0.014) and lowered the levels of IL-4 (P=0.030) and IL-5 (P=0.035) in alveolar lavage fluid. Immunohistochemical staining showed that the expressions of XBP-1 and GRP-78 in airway epithelial cells decreased significantly after the treatment of 17-AAG.
		                        		
		                        			CONCLUSIONS
		                        			HSP90α promotes HDM-induced airway allergic inflammation possibly by upregulating ER stress pathway in bronchial epithelial cells.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Asthma/metabolism*
		                        			;
		                        		
		                        			Endoplasmic Reticulum Stress
		                        			;
		                        		
		                        			Epithelial Cells
		                        			;
		                        		
		                        			Inflammation/metabolism*
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Mice, Inbred C57BL
		                        			;
		                        		
		                        			Pyroglyphidae
		                        			
		                        		
		                        	
            
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