Effect of TGF-β1 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease.

Cysteinyl leukotriene (cysLT) overproduction and eosinophil activation are hallmarks of aspirin-exacerbated respiratory disease (AERD). However, pathogenic mechanisms of AERD remain to be clarified. Here, we aimed to find the significance of transforming growth factor beta 1 (TGF-β1) in association...

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Autores principales:	Youngwoo Choi, Soyoon Sim, Dong-Hyun Lee, Hee-Ra Lee, Ga-Young Ban, Yoo Seob Shin, Yoon-Keun Kim, Hae-Sim Park
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/821a5ab853584442991b995074da7932
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spelling	oai:doaj.org-article:821a5ab853584442991b995074da79322021-12-02T20:17:33ZEffect of TGF-β1 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease.1932-620310.1371/journal.pone.0256237https://doaj.org/article/821a5ab853584442991b995074da79322021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256237https://doaj.org/toc/1932-6203Cysteinyl leukotriene (cysLT) overproduction and eosinophil activation are hallmarks of aspirin-exacerbated respiratory disease (AERD). However, pathogenic mechanisms of AERD remain to be clarified. Here, we aimed to find the significance of transforming growth factor beta 1 (TGF-β1) in association with cysteinyl leukotriene E4 (LTE4) production, leading to eosinophil degranulation. To evaluate levels of serum TGF-β1, first cohort enrolled AERD (n = 336), ATA (n = 442) patients and healthy control subjects (HCs, n = 253). In addition, second cohort recruited AERD (n = 34) and ATA (n = 25) patients to investigate a relation between levels of serum TGF-β1 and urinary LTE4. The function of TGF-β1 in LTE4 production was further demonstrated by ex vivo (human peripheral eosinophils) or in vivo (BALB/c mice) experiment. As a result, the levels of serum TGF-β1 were significantly higher in AERD patients than in ATA patients or HCs (P = .001; respectively). Moreover, levels of serum TGF-β1 and urinary LTE4 had a positive correlation (r = 0.273, P = .037). In the presence of TGF-β1, leukotriene C4 synthase (LTC4S) expression was enhanced in peripheral eosinophils to produce LTE4, which sequentially induced eosinophil degranulation via the p38 pathway. When mice were treated with TGF-β1, significantly induced eosinophilia with increased LTE4 production in the lung tissues were noted. These findings suggest that higher levels of TGF-β1 in AERD patients may contribute to LTE4 production via enhancing LTC4S expression which induces eosinophil degranulation, accelerating airway inflammation.Youngwoo ChoiSoyoon SimDong-Hyun LeeHee-Ra LeeGa-Young BanYoo Seob ShinYoon-Keun KimHae-Sim ParkPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0256237 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Youngwoo Choi Soyoon Sim Dong-Hyun Lee Hee-Ra Lee Ga-Young Ban Yoo Seob Shin Yoon-Keun Kim Hae-Sim Park Effect of TGF-β1 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease.
description	Cysteinyl leukotriene (cysLT) overproduction and eosinophil activation are hallmarks of aspirin-exacerbated respiratory disease (AERD). However, pathogenic mechanisms of AERD remain to be clarified. Here, we aimed to find the significance of transforming growth factor beta 1 (TGF-β1) in association with cysteinyl leukotriene E4 (LTE4) production, leading to eosinophil degranulation. To evaluate levels of serum TGF-β1, first cohort enrolled AERD (n = 336), ATA (n = 442) patients and healthy control subjects (HCs, n = 253). In addition, second cohort recruited AERD (n = 34) and ATA (n = 25) patients to investigate a relation between levels of serum TGF-β1 and urinary LTE4. The function of TGF-β1 in LTE4 production was further demonstrated by ex vivo (human peripheral eosinophils) or in vivo (BALB/c mice) experiment. As a result, the levels of serum TGF-β1 were significantly higher in AERD patients than in ATA patients or HCs (P = .001; respectively). Moreover, levels of serum TGF-β1 and urinary LTE4 had a positive correlation (r = 0.273, P = .037). In the presence of TGF-β1, leukotriene C4 synthase (LTC4S) expression was enhanced in peripheral eosinophils to produce LTE4, which sequentially induced eosinophil degranulation via the p38 pathway. When mice were treated with TGF-β1, significantly induced eosinophilia with increased LTE4 production in the lung tissues were noted. These findings suggest that higher levels of TGF-β1 in AERD patients may contribute to LTE4 production via enhancing LTC4S expression which induces eosinophil degranulation, accelerating airway inflammation.
format	article
author	Youngwoo Choi Soyoon Sim Dong-Hyun Lee Hee-Ra Lee Ga-Young Ban Yoo Seob Shin Yoon-Keun Kim Hae-Sim Park
author_facet	Youngwoo Choi Soyoon Sim Dong-Hyun Lee Hee-Ra Lee Ga-Young Ban Yoo Seob Shin Yoon-Keun Kim Hae-Sim Park
author_sort	Youngwoo Choi
title	Effect of TGF-β1 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease.
title_short	Effect of TGF-β1 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease.
title_full	Effect of TGF-β1 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease.
title_fullStr	Effect of TGF-β1 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease.
title_full_unstemmed	Effect of TGF-β1 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease.
title_sort	effect of tgf-β1 on eosinophils to induce cysteinyl leukotriene e4 production in aspirin-exacerbated respiratory disease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/821a5ab853584442991b995074da7932
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Effect of TGF-β1 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease.

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