Involvement of B2 Receptor in Bradykinin-Induced Proliferation and Proinflammatory Effects in Human Nasal Mucosa-Derived Fibroblasts Isolated from Chronic Rhinosinusitis Patients
| Autor: | Chih-Li Chen, Brian J. Lin, Yih-Jeng Tsai, Sheng-Po Hao, Wen-Bin Wu |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Chemokine
Stromal cell Receptor Bradykinin B2 Chemokine CXCL1 lcsh:Medicine Gene Expression Biology Bradykinin Receptor Bradykinin B1 Proinflammatory cytokine Cell Adhesion medicine Humans Interleukin 8 Sinusitis lcsh:Science Fibroblast Receptor Cells Cultured Cell Proliferation Rhinitis Multidisciplinary Cell adhesion molecule lcsh:R Interleukin-8 Fibroblasts CXCL1 Nasal Mucosa medicine.anatomical_structure Chronic Disease Immunology Cancer research biology.protein lcsh:Q Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 5, p e0126853 (2015) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0126853 |
| Popis: | Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal mucosa either accompanied by polyp formation (CRSwNP) or without polyps (CRSsNP). CRSsNP accounts for the majority of CRS cases and is characterized by fibrosis and neutrophilic inflammation. However, the pathogenesis of CRS, especially CRSsNP, remains unclear. Immunohistochemistry of CRSsNP specimens in the present study showed that the submucosa, perivascular areas, and the mucous glands were abundant in fibroblasts. Therefore, we investigated the effects bradykinin (BK), an autacoid known to participate in inflammation, on human CRSsNP nasal mucosa-derived fibroblasts (NMDFs). BK increased CXCL1 and -8 secretion and mRNA expression with EC50 ranging from 0.15~0.35 μM. Moreover, BK enhanced cell proliferation and upregulated the expressions of proinflammatory molecules, including cell adhesion molecules (CAMs) and cyclooxygenase (COX)-1 and -2. These functionally caused an increase in monocyte adhesion to fibroblast monolayer. Using pharmacological intervention and BKR siRNA knockdown, we demonstrated that the BK-induced CXCL chemokine release, cell proliferation and COX and CAM expressions were mainly through the B2 receptor (B2R). Accordingly, the B2R was preferentially expressed in the NMDFs than B1R. The B2R was highly expressed in the CRSsNP than the control specimens, while the B1R and kininogen (KNG)/BK expression slightly increased in the CRSsNP mucosa. Collectively, we report here for the first time that fibroblasts, KNG/BK, and BKRs are overexpressed in CRSsNP mucosa and BK upregulates chemokine expression, proliferation, and proinflammatory molecule expression in NMDFs via B2R activation, which lead to a functional increase in monocyte-fibroblast interaction. Our findings reveal a critical role of fibroblast, KNG/BK, and BKRs in the development of CRSsNP. |
| Databáze: | OpenAIRE |
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