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Please use this identifier to cite or link to this item:
https://ir.csmu.edu.tw:8080/ir/handle/310902500/19914
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| Title: | Epithelial growth factor receptor tyrosine kinase inhibitors alleviate house dust mite allergen Der p2-induced IL-6 and IL-8 |
| Authors: | Pan, H.-H.
Hsiao, Y.-P.
Chen, P.-J.
Kang, Y.-T.
Chao, Y.-H.
Sheu, J.-N.
Lue, K.-H.
Ko, J.-L. |
| Date: | 2019-03 |
| Issue Date: | 2019-03-19T03:15:28Z (UTC)
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| ISSN: | 15204081 |
| Abstract: | Steroid-insensitive asthma-related airway inflammation is associated with the expression of epidermal growth factor receptor (EGFR) tyrosine kinase in asthmatic bronchial epithelium. Proinflammatory cytokines IL-6 and IL-8 are related to steroid-insensitive asthma. It is currently unknown how EGFR-tyrosine kinase inhibitors (EGFR-TKIs) affects house dust mite (HDM)-induced asthma in terms of inflammatory cytokines related to steroid-resistant asthma and further signaling pathway. Cytokine expressions and EGFR signaling pathway were performed by ELISA, reverse transcriptase PCR, real-time PCR, and Western blot in cell-line models. AMP-activated protein kinase (AMPK) pathway-related inhibitors were applied to confirm the association between EGFR-TKI and AMPK pathway. HDM induced IL-6 and IL-8 in a dose-dependent manner. Both Erlotinib (Tarceva) and Osimertinib (AZD-9291) reduced the levels of HDM-stimulated IL-6 and IL-8 levels in BEAS-2B cells. AZD-9291 was more effective than Erlotinib in inhibiting phospho-EGFR, and downstream phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and phopho-signal transducer and activator of transcription 3 (p-STAT3) pathway signaling. In addition, AMPK pathway-related inhibitor, Calcium-/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, down-regulated IL-8, but EGFR-TKI had no effect on AMPK pathway. Our findings highlight EGFR-TKIs, Tarceva, and AZD-9291, attenuate HDM-induced inflammatory IL-6 and IL-8 cytokines via EGFR signaling axis pathway, but not AMPK signaling pathway. © 2019 Wiley Periodicals, Inc. |
| URI: | https://ir.csmu.edu.tw:8080/ir/handle/310902500/19914 |
| Relation: | Environmental Toxicology Volume 34, Issue 4, April 2019, Pages 476-485 |
| Appears in Collections: | [醫學系] 期刊論文
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| Epithelial-growth-factor-receptor-tyrosine-kinase-inhibitors-alleviate-house-dust-mite-allergen-Der-p2induced-IL6-and-IL82019Environmental-Toxicology.pdf | | 2610Kb | Adobe PDF | 231 | View/Open |
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