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Li M, Wang ZN, Yang LF, et al. TLR4 antagonist suppresses airway remodeling in asthma by inhibiting the T-helper 2 response. Exp Ther Med. 2017;14(4):2911-2916doi: 10.3892/etm.2017.4898.
Li, M., Wang, Z. N., Yang, L. F., Yan, Y., Cai, L. M., Li, Y. T., Qiao, Y. K., & Chen, Z. G. (2017). TLR4 antagonist suppresses airway remodeling in asthma by inhibiting the T-helper 2 response. Experimental and therapeutic medicine, 14(4), 2911-2916. https://doi.org/10.3892/etm.2017.4898
Li, Ming, et al. "TLR4 antagonist suppresses airway remodeling in asthma by inhibiting the T-helper 2 response." Experimental and therapeutic medicine vol. 14,4 (2017): 2911-2916. doi: https://doi.org/10.3892/etm.2017.4898
Li M, Wang ZN, Yang LF, Yan Y, Cai LM, Li YT, Qiao YK, Chen ZG. TLR4 antagonist suppresses airway remodeling in asthma by inhibiting the T-helper 2 response. Exp Ther Med. 2017 Oct;14(4):2911-2916. doi: 10.3892/etm.2017.4898. Epub 2017 Aug 07. PMID: 28966674; PMCID: PMC5613182.
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Exp Ther Med. 2017 Oct;14(4):2911-2916. doi: 10.3892/etm.2017.4898. Epub 2017 Aug 07.

TLR4 antagonist suppresses airway remodeling in asthma by inhibiting the T-helper 2 response.

Experimental and therapeutic medicine

Ming Li, Zhao-Ni Wang, Li-Fen Yang, Yan Yan, Liang-Ming Cai, Ya-Ting Li, Yong-Kang Qiao, Zhuang-Gui Chen

Affiliations

  1. Department of Pulmonary Diseases, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510700, P.R. China.
  2. Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China.
  3. Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore.
  4. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore.

PMID: 28966674 PMCID: PMC5613182 DOI: 10.3892/etm.2017.4898

Abstract

Airway remodeling is a hallmark of bronchial asthma. Our group has previously reported that the thymic stromal lymphopoietin (TSLP), an airway epithelial-derived cytokine, has a central role in the pathogenesis of airway remodeling, and that toll-like receptor (TLR) 4 signaling in epithelial cells may trigger T-helper 2 (Th2) immune responses by overexpression of TSLP. However, it is currently unclear whether TLR4 is a target in the treatment of airway remodeling in asthma. The present study established a house dust mite (HDM)-induced chronic asthmatic model in female BALB/c mice and treated the HDM-exposed mice with 3 mg/kg TAK242, as a TLR4 antagonist, 30 min prior to HDM challenge for up to 2 weeks. General structural changes in the airways were subsequently evaluated and the levels of TSLP in the bronchoalveolar lavage fluid (BALF) and interleukin (IL)-4, IL-13 and interferon (IFN)-γ in the blood serum were determined. Results indicated that TAK242 treatment markedly reduced pathological changes in the airways of HDM-induced asthmatic mice, as demonstrated by reductions in airway wall thickening, peribronchial collagen deposition and subepithelial fibrosis. Furthermore, airway hyperresponsiveness to inhaled methacholine and the levels of TSLP in the BALF and IL-4, IL-13 and IFN-γ in the peripheral blood were significantly reduced by TAK242 treatment (P<0.05). Furthermore, the shift in the IFN-γ/IL-4 ratio induced by HDM treatment was significantly reversed following TAK242 pretreatment, which indicated that TAK242 modulated Th1/Th2 immune homeostasis in the chronic asthma mouse model. The present findings in a chronic asthma mouse model suggest that TAK242 may be an efficient treatment for airway remodeling, possibly through the inhibition of TSLP overexpression and Th2 airway inflammation.

Keywords: airway remodeling; bronchial asthma; mouse model; thymic stromal lymphopoietin; toll-like receptor 4 antagonist

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