Liver X Receptor Expression and Pentraxin 3 Production in Chronic Rhinosinusitis and Sinonasal Mucosal Fibroblast Cells
| Autor: | Ping-Hung Shen, Yih-Jeng Tsai, Sheng-Dean Luo, Wen-Bin Wu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Agonist
medicine.drug_class pentraxin Peroxisome proliferator-activated receptor lcsh:Medicine Inflammation Article 03 medical and health sciences 0302 clinical medicine medicine otorhinolaryngologic diseases nuclear receptor 030223 otorhinolaryngology Liver X receptor Protein kinase B PI3K/AKT/mTOR pathway 030304 developmental biology PTX3 chemistry.chemical_classification 0303 health sciences PI3K/Akt business.industry lcsh:R General Medicine Nuclear receptor chemistry Cancer research LXR medicine.symptom business GW3965 |
| Zdroj: | Journal of Clinical Medicine Volume 10 Issue 3 Journal of Clinical Medicine, Vol 10, Iss 452, p 452 (2021) |
| ISSN: | 2077-0383 |
| Popis: | 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 LXR&alpha and &beta expression and lipid/fat deposition were differentially expressed in the control and CRSsNP nasal mucosa. GW7647 (a peroxisome proliferator activated receptor &alpha (PPAR&alpha ) agonist) and GW3965 (a dual agonist for LXR&alpha ) 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 LXR&alpha or &beta 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 LXR&alpha 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. |
| Databáze: | OpenAIRE |
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