- Title
- Combined treatment with SB203580 and dexamethasone suppresses non-typeable Haemophilus influenzae-induced Th17 inflammation response in murine allergic asthma
- Creator
- Wang, Guoqiang; Pang, Zhiqiang; Chen-Yu Hsu, Alan; Guan, Xuewa; Ran, Nan; Yuan, Yuke; Wang, Ziyan; Guo, Yingqiao; Zheng, Ruipeng; Wang, Fang
- Relation
- European Journal of Pharmacology Vol. 862, Issue 5 November 2019, no. 172623
- Publisher Link
- http://dx.doi.org/10.1016/j.ejphar.2019.172623
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2019
- Description
- Accumulating evidence suggests that non-typeable Haemophilus influenzae (NTHi) infection drives the development of steroid-resistant allergic airway disease (SRAAD), exacerbates clinical symptoms, worsens quality of life, and accounts for most of the related healthcare burden. The poor understanding of the pathogenesis of SRAAD deters the development of more effective therapeutic strategies. Here, we established a murine model of NTHi infection-induced exacerbation of allergic airway disease. We showed that NTHi infection drove Th 17-mediated pulmonary neutrophilic inflammation, aggravated airway hyper-responsiveness, and upset the balance of MUC5AC and MUC5B expression. Dexamethasone treatment effectively inhibited the features of allergic airway disease but failed to reduce NTHi-induced exacerbation, which was associated with the hyper-phosphorylation of p38 mitogen-activated protein kinase (MAPK). Interestingly, inhibition of p38 using a specific inhibitor (SB203580) only partly suppressed the airway hyper-responsiveness and mucus hyper-secretion but failed to abrogate the infection-induced neutrophilic inflammatory response in SRAAD. However, SB203580 and dexamethasone co-treatment substantially suppressed all the features of NTHi-induced SRAAD. Our findings highlight the importance of p38 MAPK in the pathogenesis of NTHi-induced steroid resistance, and this combined treatment approach may be a novel strategy against steroid-resistant asthma.
- Subject
- steroid-resistant asthma; airway hyper-responsiveness; non-typeable haemophilus influenzae; Th17 inflammation response; p38 MAPK; SB203580
- Identifier
- http://hdl.handle.net/1959.13/1425300
- Identifier
- uon:38228
- Identifier
- ISSN:0014-2999
- Language
- eng
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