Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthma
Background/Aims Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a key role in Th2-mediated inflammation, both directly by promoting the proliferation of naïve CD4 Th2 cells, and indirectly by activating dendritic cells (DCs). TSLP-activated DCs induce the expans...
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doaj-3761b7ff190e4d44aeb169e81c0748442021-08-10T04:41:12ZengThe Korean Association of Internal MedicineThe Korean Journal of Internal Medicine1226-33032005-66482020-05-0135361962910.3904/kjim.2018.248170332Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthmaHea Yon Lee0Hwa Young Lee1Jung Hur2Hye Seon Kang3Joon Young Choi4Chin Kook Rhee5Ji Young Kang6Young Kyoon Kim7Sook Young Lee8 Department of Health Promotion Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, KoreaBackground/Aims Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a key role in Th2-mediated inflammation, both directly by promoting the proliferation of naïve CD4 Th2 cells, and indirectly by activating dendritic cells (DCs). TSLP-activated DCs induce the expansion of chemoattractant receptor homologous molecule expressed on Th2 (CRTH2)+ CD4+ Th2 memory cells, which undergo a Th2 response and express prostaglandin D2 (PGD2) synthase. CRTH2, a PGD2 receptor, is a selective Th2-cell surface marker. We investigated the effects of an anti-TSLP antibody (Ab) and a CRTH2 antagonist, as well as their mechanisms of action, in a mouse model of acute asthma. Methods BALB/c mice were sensitized and challenged with ovalbumin. We then evaluated the effects of the administration of an anti-TSLP Ab either alone or together with a CRTH2 antagonist on cell counts, Th2 cytokine levels in bronchoalveolar fluid, and the levels of epithelium-derived cytokines such as TSLP, interleukin (IL) 33, and IL-25 in lung homogenates, as well as airway hyper-responsiveness (AHR). Results Anti-TSLP Ab and the CRTH2 antagonist significantly attenuated eosinophilic airway inflammation, AHR, and the expression of Th2 cytokines. The expression of GATA-3 and the levels of IL-33 and IL-25 in lung tissues were affected by the combined anti-TSLP and CRTH2 antagonist treatment. Conclusions These results suggest that the dual blockade of TSLP and CRTH2 may serve as an effective treatment target for eosinophilic asthma.http://www.kjim.org/upload/pdf/kjim-2018-248.pdfasthmathymic stromal lymphopoietinairway resistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hea Yon Lee Hwa Young Lee Jung Hur Hye Seon Kang Joon Young Choi Chin Kook Rhee Ji Young Kang Young Kyoon Kim Sook Young Lee |
spellingShingle |
Hea Yon Lee Hwa Young Lee Jung Hur Hye Seon Kang Joon Young Choi Chin Kook Rhee Ji Young Kang Young Kyoon Kim Sook Young Lee Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthma The Korean Journal of Internal Medicine asthma thymic stromal lymphopoietin airway resistance |
author_facet |
Hea Yon Lee Hwa Young Lee Jung Hur Hye Seon Kang Joon Young Choi Chin Kook Rhee Ji Young Kang Young Kyoon Kim Sook Young Lee |
author_sort |
Hea Yon Lee |
title |
Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthma |
title_short |
Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthma |
title_full |
Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthma |
title_fullStr |
Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthma |
title_full_unstemmed |
Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthma |
title_sort |
blockade of thymic stromal lymphopoietin and crth2 attenuates airway inflammation in a murine model of allergic asthma |
publisher |
The Korean Association of Internal Medicine |
series |
The Korean Journal of Internal Medicine |
issn |
1226-3303 2005-6648 |
publishDate |
2020-05-01 |
description |
Background/Aims Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a key role in Th2-mediated inflammation, both directly by promoting the proliferation of naïve CD4 Th2 cells, and indirectly by activating dendritic cells (DCs). TSLP-activated DCs induce the expansion of chemoattractant receptor homologous molecule expressed on Th2 (CRTH2)+ CD4+ Th2 memory cells, which undergo a Th2 response and express prostaglandin D2 (PGD2) synthase. CRTH2, a PGD2 receptor, is a selective Th2-cell surface marker. We investigated the effects of an anti-TSLP antibody (Ab) and a CRTH2 antagonist, as well as their mechanisms of action, in a mouse model of acute asthma. Methods BALB/c mice were sensitized and challenged with ovalbumin. We then evaluated the effects of the administration of an anti-TSLP Ab either alone or together with a CRTH2 antagonist on cell counts, Th2 cytokine levels in bronchoalveolar fluid, and the levels of epithelium-derived cytokines such as TSLP, interleukin (IL) 33, and IL-25 in lung homogenates, as well as airway hyper-responsiveness (AHR). Results Anti-TSLP Ab and the CRTH2 antagonist significantly attenuated eosinophilic airway inflammation, AHR, and the expression of Th2 cytokines. The expression of GATA-3 and the levels of IL-33 and IL-25 in lung tissues were affected by the combined anti-TSLP and CRTH2 antagonist treatment. Conclusions These results suggest that the dual blockade of TSLP and CRTH2 may serve as an effective treatment target for eosinophilic asthma. |
topic |
asthma thymic stromal lymphopoietin airway resistance |
url |
http://www.kjim.org/upload/pdf/kjim-2018-248.pdf |
work_keys_str_mv |
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