Inhibition of arachidonate 15-lipoxygenase reduces the epithelial-mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps.
Adult
Aged
Arachidonate 15-Lipoxygenase
/ metabolism
Arachidonic Acid
/ metabolism
Cells, Cultured
Chronic Disease
Eosinophils
/ immunology
Epithelial-Mesenchymal Transition
Female
Fluorenes
/ pharmacology
Humans
Lipoxygenase Inhibitors
/ pharmacology
Male
Matrix Metalloproteinase 1
/ genetics
Middle Aged
Nasal Polyps
/ metabolism
Rhinitis
/ metabolism
Sinusitis
/ metabolism
Tissue Inhibitor of Metalloproteinase-1
/ metabolism
Transforming Growth Factor beta3
/ genetics
BM
CRSwNP
EMT
MMP
TIMP
airway remodeling
arachidonate 15-lipoxygenase
basement membrane
chronic rhinosinusitis with nasal polyps
epithelial-mesenchymal transition
metalloproteinases
tight junction proteins
tissue inhibitor of metalloproteinase
Journal
International forum of allergy & rhinology
ISSN: 2042-6984
Titre abrégé: Int Forum Allergy Rhinol
Pays: United States
ID NLM: 101550261
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
31
05
2018
revised:
05
10
2018
accepted:
17
10
2018
pubmed:
20
11
2018
medline:
18
1
2020
entrez:
20
11
2018
Statut:
ppublish
Résumé
The epithelial-mesenchymal transition (EMT) is a distinguishing characteristic of chronic rhinosinusitis with nasal polyps (CRSwNP). The underlying mechanism remains largely unknown. Arachidonate 15-lipoxygenase (ALOX15), an enzyme involved in arachidonic acid metabolism, has been reported to cause airway epithelial injury and thus may further promote the EMT. The aim of this study was to evaluate the role of ALOX15 during the EMT process in CRSwNP. A total of 54 samples were obtained, including 10 from healthy control, 16 from non-eosinophilic CRSwNP, and 28 from eosinophilic CRSwNP. Hematoxylin and eosin staining was performed to determine the basement membrane (BM) thickness. The concentration of molecules mediating remodeling was assayed by Luminex. The messenger RNA (mRNA) and protein levels of target genes were measured by quantitative real-time polymerase chain reaction (PCR) and Western blotting. EMT was enhanced in eosinophilic CRSwNP compared with the healthy controls and non-eosinophilic CRSwNP infiltrated with lymphocytes and/or plasma cells. The expression pattern of molecules related to remodeling, including matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and transforming growth factor β (TGF-β) family members, differed between the subtypes of CRSwNP. The mRNA level of ALOX15 was correlated with the BM thickness and MMP-1 and TGF-β3 expression. The inhibition of ALOX15 by PD146176 could induce claudin-1, claudin-4, claudin-7, zonula occludens (ZO)-1, ZO-2, E-Cadherin, TIMP-1, and TIMP-3 expressions and reduce the levels of MMP-1 and N-Cadherin in epithelial cells acquired from eosinophilic CRSwNP patients. The specific inhibition of ALOX15 could attenuate the EMT, which may provide an alternative method for the treatment of CRSwNP.
Sections du résumé
BACKGROUND
The epithelial-mesenchymal transition (EMT) is a distinguishing characteristic of chronic rhinosinusitis with nasal polyps (CRSwNP). The underlying mechanism remains largely unknown. Arachidonate 15-lipoxygenase (ALOX15), an enzyme involved in arachidonic acid metabolism, has been reported to cause airway epithelial injury and thus may further promote the EMT. The aim of this study was to evaluate the role of ALOX15 during the EMT process in CRSwNP.
METHODS
A total of 54 samples were obtained, including 10 from healthy control, 16 from non-eosinophilic CRSwNP, and 28 from eosinophilic CRSwNP. Hematoxylin and eosin staining was performed to determine the basement membrane (BM) thickness. The concentration of molecules mediating remodeling was assayed by Luminex. The messenger RNA (mRNA) and protein levels of target genes were measured by quantitative real-time polymerase chain reaction (PCR) and Western blotting.
RESULTS
EMT was enhanced in eosinophilic CRSwNP compared with the healthy controls and non-eosinophilic CRSwNP infiltrated with lymphocytes and/or plasma cells. The expression pattern of molecules related to remodeling, including matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and transforming growth factor β (TGF-β) family members, differed between the subtypes of CRSwNP. The mRNA level of ALOX15 was correlated with the BM thickness and MMP-1 and TGF-β3 expression. The inhibition of ALOX15 by PD146176 could induce claudin-1, claudin-4, claudin-7, zonula occludens (ZO)-1, ZO-2, E-Cadherin, TIMP-1, and TIMP-3 expressions and reduce the levels of MMP-1 and N-Cadherin in epithelial cells acquired from eosinophilic CRSwNP patients.
CONCLUSION
The specific inhibition of ALOX15 could attenuate the EMT, which may provide an alternative method for the treatment of CRSwNP.
Substances chimiques
6,11-dihydro-5-thia-11-aza-benzo(a)-fluorene
0
Fluorenes
0
Lipoxygenase Inhibitors
0
Tissue Inhibitor of Metalloproteinase-1
0
Transforming Growth Factor beta3
0
Arachidonic Acid
27YG812J1I
Arachidonate 15-Lipoxygenase
EC 1.13.11.33
Matrix Metalloproteinase 1
EC 3.4.24.7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
270-280Informations de copyright
© 2018 ARS-AAOA, LLC.