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Expression of long pentraxin 3 in human nasal mucosa fibroblasts, tissues, and secretions of chronic rhinosinusitis without nasal polyps

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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.

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Abbreviations

CREB:

cAMP response element binding protein

CRSsNP:

Chronic rhinosinusitis without nasal polyps

CRSwNP:

Chronic rhinosinusitis with nasal polyps

PI-PLC:

Phosphoinositide-phospholipase C

PKC:

Protein kinase C

PTX3:

Pentraxin 3

PGN:

Peptidoglycan

TLR :

Toll-like receptor

hNMDFs:

Human nasal mucosa-derived fibroblasts

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Funding

This work was supported by the grant from Ministry of Science and Technology in Taiwan (MOST 105-2320-B-030-005).

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Authors and Affiliations

  1. School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

    Yih-Jeng Tsai, Chih-Li Chen, Pi-Hui Wu & Wen-Bin Wu

  2. Department of Otolaryngology Head and Neck Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Yih-Jeng Tsai & Chung-Yu Hao

  3. Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City, 24205, Taiwan

    Wen-Bin Wu

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  1. Yih-Jeng Tsai
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Correspondence to Wen-Bin Wu.

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This study was approved by the Ethics Committee of the Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, and conducted with the written informed consent of the patients.

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Tsai, YJ., Hao, CY., Chen, CL. et al. Expression of long pentraxin 3 in human nasal mucosa fibroblasts, tissues, and secretions of chronic rhinosinusitis without nasal polyps. J Mol Med 98, 673–689 (2020). https://doi.org/10.1007/s00109-020-01899-7

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