Epithelial growth factor receptor tyrosine kinase inhibitors alleviate house dust mite allergen Der p2‐induced IL‐6 and IL‐8. Issue 4 (8th January 2019)

• Record Type: Journal Article
• Authors: Pan, Hui‐Hsien; Hsiao, Yu‐Ping; Chen, Ping‐Ju; Kang, Yu‐Ting; Chao, Yu‐Hua; Sheu, Ji‐Nan; Lue, Ko‐Huang; Ko, Jiunn‐Liang
• Is Part Of: Environmental toxicology. Volume 34:Issue 4(2019)
• Page Start: 476
• Page End: 485
• Publication Date: 2019-01-08
• Subjects: AMPK -- Dermatophagoides pteronyssinus -- EGFR‐TKIs -- IL‐6 -- IL‐8; Water quality bioassay -- Periodicals; Water -- Pollution -- Toxicology -- Periodicals; Microbiological assay -- Periodicals; Toxicity testing -- Periodicals; Environmental toxicology -- Periodicals; Environmental Pollution -- Periodicals; Environmental Pollutants -- Periodicals; Environmental Monitoring -- Periodicals; Écotoxicologie -- Périodiques; Pollution -- Périodiques; 615.902
• DOI: 10.1002/tox.22701
• Languages: English
• ISSNs: 1520-4081

Abstract

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.