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Expression of long pentraxin 3 in human nasal mucosa fibroblasts, tissues, and secretions of chronic rhinosinusitis without nasal polyps.
Expression of long pentraxin 3 in human nasal mucosa fibroblasts, tissues, and secretions of chronic rhinosinusitis without nasal polyps.
- Source :
-
Journal of molecular medicine (Berlin, Germany) [J Mol Med (Berl)] 2020 May; Vol. 98 (5), pp. 673-689. Date of Electronic Publication: 2020 Apr 02. - Publication Year :
- 2020
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Abstract
- Numerous studies have shown that microbiomes play an important role in the pathogenesis of chronic rhinosinusitis (CRS). In addition to a known short pentraxin, C-reactive protein, long pentraxin 3 (PTX3) belongs to pentraxin family which detects conserved microbial pentraxin motifs and mobilizes early defense against foreign invaders, but its participation in CRS remains unclear. In the present study, through an intensive screening, peptidoglycan (PGN) was selected as a main material to investigate the action mechanism of a cell wall component on CRS without nasal polyps (CRSsNP) nasal mucosa-derived fibroblasts and the PTX3 expression in human nasal mucosa tissue and discharge. The PGN not only enhanced PTX3 mRNA and protein production in cells but also caused marked PTX3 secretion into extracellular space. The pharmacological interventions indicated that the PTX3 induction was mediated mainly through toll-like receptor 2 (TLR2), phosphoinositide-phospholipase C (PI-PLC), protein kinase C (PKC), NF-κB, and cAMP response element binding protein (CREB), which was further confirmed by the observations that a direct PKC activator (phorbol ester) had a similar inductory effect on PTX3 expression/production and the siRNA interference knockdown of PKCμ/δ, NF-κB, and CREB compromised PTX3 production. Meanwhile, PTX3 was found to be overexpressed/produced in nasal mucosa and discharge/secretion of the CRSsNP patients. Collectively, we first demonstrated here that PGN enhances PTX3 expression and release in nasal fibroblasts through TLR2, PI-PLC, PKCμ/δ, NF-κB, and CREB signaling pathways. The PTX3 is overexpressed in nasal mucosa and discharge/secretion of CRSsNP patients, revealing its possible importance in CRSsNP development and progression. KEY MESSAGES: Long pentraxin 3 (PTX3) is highly expressed in nasal mucosa and discharge/secretion of patients of chronic rhinosinusitis without nasal polyps (CRSsNP). The bacteria cell wall component-peptidoglycan (PGN) causes PTX3 expression in CRSsNP nasal mucosa-derived fibroblasts, contributing to the PTX3 increase in tissues. PGN induces PTX3 expression through a previously known IκB/NF-κB and a novel PKCμ/δ and CREB signaling pathway. The PTX3 may be used as a biomarker for CRS.
- Subjects :
- Biomarkers
C-Reactive Protein metabolism
Cells, Cultured
Cyclic AMP Response Element-Binding Protein metabolism
Cytokines metabolism
Disease Susceptibility
Extracellular Space
Fibroblasts metabolism
Humans
I-kappa B Proteins metabolism
Inflammation Mediators metabolism
NF-kappa B metabolism
Nasal Mucosa pathology
Protein Kinase C metabolism
RNA, Small Interfering genetics
Serum Amyloid P-Component metabolism
Signal Transduction
C-Reactive Protein genetics
Gene Expression
Nasal Mucosa metabolism
Nasal Polyps pathology
Rhinitis etiology
Rhinitis pathology
Serum Amyloid P-Component genetics
Sinusitis etiology
Sinusitis pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-1440
- Volume :
- 98
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of molecular medicine (Berlin, Germany)
- Publication Type :
- Academic Journal
- Accession number :
- 32239253
- Full Text :
- https://doi.org/10.1007/s00109-020-01899-7