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- Title
IL-4-induced caveolin-1-containing lipid rafts aggregation contributes to MUC5AC synthesis in bronchial epithelial cells.
- Authors
Yu Xia; Peng-Cheng Cai; Fan Yu; Liang Xiong; Xin-Liang He; Shan-Shan Rao; Feng Chen; Xiang-Ping Yang; Wan-Li Ma; Hong Ye; Xia, Yu; Cai, Peng-Cheng; Yu, Fan; Xiong, Liang; He, Xin-Liang; Rao, Shan-Shan; Chen, Feng; Yang, Xiang-Ping; Ma, Wan-Li; Ye, Hong
- Abstract
<bold>Background: </bold>Mucus overproduction is an important feature of asthma. Interleukin (IL)-4 is required for allergen-induced airway inflammation and mucus production. MUC5AC gene expression is regulated by transcript factors NF-κB. The intracellular Ca2+ ([Ca2+]i) signal is required for activation of NF-κB. The transient receptor potential canonical 1 (TRPC1) channel has been shown to contribute for agonist-stimulated Ca2+ influx in some types of cells. However, the relationships among IL-4, TRPC1 and mucus overproduction in bronchial epithelial cells (BECs) in asthma are poorly understood.<bold>Methods: </bold>BECs were isolated from large bronchial airway of rats and used as cell model. To present changes of lipid raft, caveolin-1 and TRPC1, immunofluorescence staining and sucrose gradient centrifugation were performed. [Ca2+]i was measured after loading with Fura-2. NF-κB activities were measured by an ELISA-based assay. MUC5AC mRNA and protein levels were detected by real-time quantitative RT-PCR, ELISA analysis and immunofluorescence staining respectively.<bold>Results: </bold>IL-4 induced Ca2+ influx in BECs, and this was blocked by a Ca2+ influx inhibitor (2-APB). 2-APB also prevented MUC5AC protein synthesis induced by IL-4. Depletion of extracellular Ca2+ resulted in partial decrease in expression of MUC5AC in IL-4 treated cells. NF-κB rather than STAT6 activation mediated IL-4-induced MUC5AC protein synthesis. Then the mechanism of Ca2+ influx was investigated. Immunofluorescence staining and sucrose gradient centrifugation revealed that caveolin-1-containing lipid rafts aggregation was involved in TRPC1 activation and Ca2+ influx in BECs. Lastly, the data revealed that blocking lipid rafts aggregation exactly prevented Ca2+ influx, NF-κB activation and MUC5AC synthesis induced by IL-4.<bold>Conclusions: </bold>Our results indicate that IL-4-induced caveolin-1-containing lipid rafts aggregation at least partly contributes to MUC5AC synthesis in BECs.
- Subjects
CAVEOLINS; LIPID rafts; GENE expression; MUCUS; ASTHMA; INTRACELLULAR calcium; EPITHELIAL cells; ANIMAL experimentation; CARRIER proteins; CELL culture; CELL membranes; GLYCOPROTEINS; INTERLEUKINS; RATS; RESPIRATORY mucosa
- Publication
Respiratory Research, 2017, Vol 18, p1
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/s12931-017-0657-z