Liver X Receptor Expression and Pentraxin 3 Production in Chronic Rhinosinusitis and Sinonasal Mucosal Fibroblast Cells
The long pentraxin 3 (PTX3) is a prototypic molecule for recognizing pathogens. Liver X receptors (LXRs), belonging to nuclear receptors (NRs) for cholesterol metabolism through heterodimerizing with other NRs, were recently reported to participate in inflammation. However, their roles in chronic rh...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-01-01
|
Series: | Journal of Clinical Medicine |
Subjects: | |
Online Access: | https://www.mdpi.com/2077-0383/10/3/452 |
id |
doaj-6b8a28061cd34cf88d2f2612acfbd6c9 |
---|---|
record_format |
Article |
spelling |
doaj-6b8a28061cd34cf88d2f2612acfbd6c92021-01-26T00:01:59ZengMDPI AGJournal of Clinical Medicine2077-03832021-01-011045245210.3390/jcm10030452Liver X Receptor Expression and Pentraxin 3 Production in Chronic Rhinosinusitis and Sinonasal Mucosal Fibroblast CellsYih-Jeng Tsai0Ping-Hung Shen1Sheng-Dean Luo2Wen-Bin Wu3Department of Otolaryngology Head and Neck Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, TaiwanDepartment of Otolaryngology, Kuang-Tien General Hospital, Taichung 43303, TaiwanDepartment of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833253, TaiwanSchool of Medicine, Fu Jen Catholic University, New Taipei City 242062, TaiwanThe long pentraxin 3 (PTX3) is a prototypic molecule for recognizing pathogens. Liver X receptors (LXRs), belonging to nuclear receptors (NRs) for cholesterol metabolism through heterodimerizing with other NRs, were recently reported to participate in inflammation. However, their roles in chronic rhinosinusitis without nasal polyps (CRSsNP) are unclear. Therefore, this study was sought to explore roles of LXRs in chronic rhinosinusitis (CRS) sinonasal tissues and derived fibroblasts. Immunohistochemistry indicated that LXRα and β expression and lipid/fat deposition were differentially expressed in the control and CRSsNP nasal mucosa. GW7647 (a peroxisome proliferator activated receptor α (PPARα) agonist) and GW3965 (a dual agonist for LXRα and β) significantly caused PTX3 induction in the fibroblast cells. GW3965 induced PTX3 mRNA and protein expression, and the induction substantially led to PTX3 secretion. Meanwhile, an endogenous agonist-cholesterol had a similar enhancing effect on the induction of PTX3 protein. LXR siRNA knockdown to lower LXRα or β expression significantly compromised PTX3 induction. Interestingly, GW3965 also induced phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) activation and its inhibition reduced PTX3 expression. Collectively, we demonstrated here for the first time that CRSsNP nasal mucosa differentially expresses LXRα and β and deposits lipids/fats that may contain cholesterol metabolites to activate LXRs. Activation of LXRs leads to PTX3 production in sinonasal mucosa-derived fibroblasts. Our previous study showed PTX3 overexpression in the nasal cavity of CRSsNP, whereas this study highlights that cholesterol metabolites and LXR activation regulate PTX3 production and may contribute to antimicrobial activity and tissue repair during CRSsNP progression.https://www.mdpi.com/2077-0383/10/3/452GW3965LXRnuclear receptorpentraxinPTX3PI3K/Akt |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yih-Jeng Tsai Ping-Hung Shen Sheng-Dean Luo Wen-Bin Wu |
spellingShingle |
Yih-Jeng Tsai Ping-Hung Shen Sheng-Dean Luo Wen-Bin Wu Liver X Receptor Expression and Pentraxin 3 Production in Chronic Rhinosinusitis and Sinonasal Mucosal Fibroblast Cells Journal of Clinical Medicine GW3965 LXR nuclear receptor pentraxin PTX3 PI3K/Akt |
author_facet |
Yih-Jeng Tsai Ping-Hung Shen Sheng-Dean Luo Wen-Bin Wu |
author_sort |
Yih-Jeng Tsai |
title |
Liver X Receptor Expression and Pentraxin 3 Production in Chronic Rhinosinusitis and Sinonasal Mucosal Fibroblast Cells |
title_short |
Liver X Receptor Expression and Pentraxin 3 Production in Chronic Rhinosinusitis and Sinonasal Mucosal Fibroblast Cells |
title_full |
Liver X Receptor Expression and Pentraxin 3 Production in Chronic Rhinosinusitis and Sinonasal Mucosal Fibroblast Cells |
title_fullStr |
Liver X Receptor Expression and Pentraxin 3 Production in Chronic Rhinosinusitis and Sinonasal Mucosal Fibroblast Cells |
title_full_unstemmed |
Liver X Receptor Expression and Pentraxin 3 Production in Chronic Rhinosinusitis and Sinonasal Mucosal Fibroblast Cells |
title_sort |
liver x receptor expression and pentraxin 3 production in chronic rhinosinusitis and sinonasal mucosal fibroblast cells |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2021-01-01 |
description |
The long pentraxin 3 (PTX3) is a prototypic molecule for recognizing pathogens. Liver X receptors (LXRs), belonging to nuclear receptors (NRs) for cholesterol metabolism through heterodimerizing with other NRs, were recently reported to participate in inflammation. However, their roles in chronic rhinosinusitis without nasal polyps (CRSsNP) are unclear. Therefore, this study was sought to explore roles of LXRs in chronic rhinosinusitis (CRS) sinonasal tissues and derived fibroblasts. Immunohistochemistry indicated that LXRα and β expression and lipid/fat deposition were differentially expressed in the control and CRSsNP nasal mucosa. GW7647 (a peroxisome proliferator activated receptor α (PPARα) agonist) and GW3965 (a dual agonist for LXRα and β) significantly caused PTX3 induction in the fibroblast cells. GW3965 induced PTX3 mRNA and protein expression, and the induction substantially led to PTX3 secretion. Meanwhile, an endogenous agonist-cholesterol had a similar enhancing effect on the induction of PTX3 protein. LXR siRNA knockdown to lower LXRα or β expression significantly compromised PTX3 induction. Interestingly, GW3965 also induced phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) activation and its inhibition reduced PTX3 expression. Collectively, we demonstrated here for the first time that CRSsNP nasal mucosa differentially expresses LXRα and β and deposits lipids/fats that may contain cholesterol metabolites to activate LXRs. Activation of LXRs leads to PTX3 production in sinonasal mucosa-derived fibroblasts. Our previous study showed PTX3 overexpression in the nasal cavity of CRSsNP, whereas this study highlights that cholesterol metabolites and LXR activation regulate PTX3 production and may contribute to antimicrobial activity and tissue repair during CRSsNP progression. |
topic |
GW3965 LXR nuclear receptor pentraxin PTX3 PI3K/Akt |
url |
https://www.mdpi.com/2077-0383/10/3/452 |
work_keys_str_mv |
AT yihjengtsai liverxreceptorexpressionandpentraxin3productioninchronicrhinosinusitisandsinonasalmucosalfibroblastcells AT pinghungshen liverxreceptorexpressionandpentraxin3productioninchronicrhinosinusitisandsinonasalmucosalfibroblastcells AT shengdeanluo liverxreceptorexpressionandpentraxin3productioninchronicrhinosinusitisandsinonasalmucosalfibroblastcells AT wenbinwu liverxreceptorexpressionandpentraxin3productioninchronicrhinosinusitisandsinonasalmucosalfibroblastcells |
_version_ |
1724323697849794560 |