HSP90α exacerbates house dust mite-induced asthmatic airway inflammation by upregulating endoplasmic reticulum stress in bronchial epithelial cells / 南方医科大学学报

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.

Clinical value of heat shock protein-90α on diagnosis, prediction of treatment response, and monitoring of relapse in breast cancer / 中国肿瘤临床

To explore the prognostic value of heat shock protein-90α (HSP-90α) plasma levels on breast cancer and non-breast malignant tumors, monitoring the response of chemotherapy, and the predictive value of cancer recurrence and metastasis. Methods: A total of 615 female patients were enrolled between June 2016 and September 2016 in Cancer Hospital, Chinese Academy of Medical Sciences, who were divided into the examination (n=389) and control (n=216) groups. The former group consisted of static (n=289) and dynamic (n=110) groups, which were analyzed by stages, histological and molecular type, and so on. The latter group in-cluded healthy people (n=103), and those with breast benign tumors (n=51) and non-breast malignant tumors (n=62). In all the plasma samples, HSP-90α was detected using a double-antibody enzyme-linked immunosorbent assay. The receiving-operating characteristic curve was used to analyze the effectiveness of plasma HSP-90α in the diagnosis of breast cancer. Wilcoxon＇s rank test and the Kruskal-Wallis test were used to analyze the association between clinical characteristics and levels of plasma HSP-90α. Results: The levels of plasma HSP-90α were significantly higher in patients with breast cancer than in healthy controls (P<0.001). When the cut-off value was set as 59.7 ng/mL for the diagnosis of breast cancer and 43.22 ng/mL for disease recurrence, the areas under the curve were 0.834 and 0.877, sensitivities were 90.3% and 95.7%, and specificities were 78.6% and 74.5%, respectively. The levels of plasma HSP-90α sig-nificantly decreased after achieving a response to neoadjuvant chemotherapy or surgery (P<0.05). Conclusions: Plasma HSP-90α has good clinical value in the diagnosis and monitoring of response and recurrence in breast cancer.

Establishment of quantitative fluorescence immunochromatographic assay detection method for heat shock protein 90α(HSP90α) / 中国免疫学杂志

Objective:To establish quantitative a fluorescence immunochromatographic assay detection method for the heat shock protein 90α(HSP90α)in human serum.Methods: Indirect the technology of fluorescence microshers immunochromatographic assay was used to research fluorescent microsphere activation,ensure optimal testing time,determine linearity range,precision,recovery experiments,testing clinical samples and that sort of thing in the fluorescence immunochromatographicassay experiment.Results: In all the reaction conditions,it was determined that the optimal teaction time was 5 minutes,and in the best line range (0.39-100 ng/ml) precision quality control materials of high recovery (30 ng/ml) Intra-assay CV was 8.14%;quality control materials of low recovery (10 ng/ml) Intra-assay CV was 9.26%.With high,medium and low recovery of serum recovery was 100.56%,99.76%,94.1%,separately.Foreign kit(ELISA) for detection of 40 cancer patients clinical serum,the result showed that the correlation was 0.968 5.Conclusion: Establishing the method initially quantitative fluorescence immunochromatographic assay for the heat shock protein 90α(HSP90α)in human serum have high performance and linear,clinic accordance rate also can satisfy the demand of clinic quantitative detection,and will improve hopeful to applied to clinic after apprroved.