Tc17/IL-17A Up-Regulated the Expression of MMP-9 via NF-κB Pathway in Nasal Epithelial Cells of Patients With Chronic Rhinosinusitis

Chen, Xiaohong; Chang, Lihong; Li, Xia; Huang, Jun; Yang, Luoying; Lai, Xiaoping; Huang, Zizhen; Wang, Zhiyuan; Wu, Xifu; Zhao, Jun; Bellanti, Joseph A.; Zheng, Song Guo; Zhang, Gehua

doi:10.3389/fimmu.2018.02121

Cited by 47 publications

(51 citation statements)

References 67 publications

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“…The EMT process is driven by an array of factors such as WNT, reactive oxygen species, proteases, HIF1, IL-13 Epiregulin, Oncostatin M, and IL-1 (Oyer et al, 2013;Batzakakis et al, 2014;Schleimer, 2017;Aazami et al, 2018;Yang et al, 2018;Tomaszewska et al, 2019). CRSwNP patients have altered expression levels of EMT related factors, such as MMP-1 (Malinsky et al, 2013;Homma et al, 2017), MMP-2 (Malinsky et al, 2013), TIMP-1 (Wang et al, 2012;Muluk et al, 2015), MMP-7 (Yang et al, 2017;Chen et al, 2018), MMP-9 (Wang et al, 2012;Malinsky et al, 2013;Yeo et al, 2013;Li et al, 2015;Muluk et al, 2015;Chen et al, 2018;Suzuki et al, 2018;Xiang et al, 2019), TIMP-2 (Li et al, 2015) E-cadherin (Hupin et al, 2014;Kim et al, 2018;Deng et al, 2019). BMT is associated with duration of inflammation independent of tissue eosinophilia (Kountakis et al, 2004;Kuhar et al, 2017).…”

Section: Upper Airway Epithelial Functions During Ar and Crsmentioning

confidence: 99%

Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases

Laulajainen‐Hongisto

Toppila‐Salmi

Luukkainen

et al. 2020

Front. Cell Dev. Biol.

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Allergic rhinitis, chronic rhinosinusitis, and asthma are highly prevalent, multifactorial chronic airway diseases. Several environmental and genetic factors affect airway epithelial dynamics leading to activation of inflammatory mechanisms in the airways. This review links environmental factors to host epithelial immunity in airway diseases. Understanding altered homeostasis of the airway epithelium might provide important targets for diagnostics and therapy of chronic airway diseases.

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Section: Upper Airway Epithelial Functions During Ar and Crsmentioning

confidence: 99%

Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases

Laulajainen‐Hongisto

Toppila‐Salmi

Luukkainen

et al. 2020

Front. Cell Dev. Biol.

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“…Western blotting was performed as reported previously. [13] The PVDF membranes were rst incubated with primary antibodies MMP-9 (1:1000; Abcam, Cambridge, UK), pERK, ERK, pIκBα, IκBα (1:1000; Cell Signaling Technology, Boston, USA), and GAPDH (1:3000; PeproTech, Rocky Hill, USA) overnight at 4 °C separately, and then incubated with HRP-conjugated secondary antibody (Bioworld, Nanjing, China). Color development was achieved by ECL reagents.…”

Section: Western Blotmentioning

confidence: 99%

“…[10] However, MMP-1, MMP-2, and MMP-3 expression in patients with CRS is controversial, whereas several studies have reported MMP-7 and MMP-9 levels to be higher in cases with CRSwNP. [11][12][13][14] Overall, the detailed upstream modulation of MMPs promoting tissue remodeling in chronic sinusitis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

IL-19 Induced by IL-13/IL-17A in the Nasal Epithelium of Patients with Chronic Rhinosinusitis Upregulates MMP-9 Expression via ERK/NF-kB Signaling Pathway

Huang

Chen

et al. 2020

Preprint

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Background: Tissue remodeling is a crucial characteristic of chronic rhinosinusitis (CRS). Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is crucial for the pathologic tissue remodeling in CRS. Elevation of interleukin (IL)-19 or MMP-9 levels in patients with CRS had been proven in previous studies. Here, we aimed to investigate the role of IL-19 in mediating MMP-9 expression in CRS. Methods: Nasal tissue samples were collected from 45 individuals having chronic rhinosinusitis with nasal polyps (CRSwNP), 24CRS without nasal polyps (CRSsNP), and 17 controls. Expression of IL-19, its receptors (IL-20R1/IL-20R2), and MMP-9 were investigated using RT-qPCR and Immunofluorescence. Human nasal epithelial cells (HNECs) were stimulated by IL-19; ERK phosphorylation, NF-kB pathway activation, and MMP-9 level were detected by RT-qPCR, ELISA, western blot and Immunofluorescence. We also explored the effect of type1/2/3 cytokines on IL-19 production by RT-qPCR, and western blot. Results: Expression levels of IL-19, its receptors (IL-20R1/IL-20R2), and MMP-9 were increased in nasal tissues from individuals with CRSwNP compared to those with CRSsNP as well as the controls. IL-19 significantly elevated the production of MMP-9 in HNECs. Furthermore, IL-19 could activate the ERK and NF-kB pathways, accompanied by increased MMP-9 production in HNECs. Conversely, both ERK and NF-kB inhibitors significantly attenuated the role of IL-19 in MMP-9 production. siRNA knockdown of IL-20R1 suppressed ERK and NF-kB pathway activation, thereby decreasing MMP-9 expression. IL-13 and IL-17A were found to stimulate IL-19 production in HNECs.Conclusion: IL-19, promoted by IL-13 and IL-17A, contributes to the upregulation of secretion of the tissue remodeling factor MMP-9 in patients with CRS.

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“…Several studies have demonstrated a relationship between CRSwNP and the NF-κB pathway. (Chen et al, 2018;Jung et al, 2019). Chen et al found that interleukin (IL)-17A upregulated the expression of matrix metalloproteinase (MMP)-9 via the NF-κB pathway in nasal epithelial cells (Chen et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…(Chen et al, 2018;Jung et al, 2019). Chen et al found that interleukin (IL)-17A upregulated the expression of matrix metalloproteinase (MMP)-9 via the NF-κB pathway in nasal epithelial cells (Chen et al, 2018). Jung et al showed that p65 NF-κB and NF-κB-related in ammatory cytokines were expressed in both eosinophilic and non-eosinophilic nasal polyps.…”

Section: Introductionmentioning

confidence: 99%

Yap Promotes Epithelial Cell Proliferation and Epithelium-derived Innate Cytokine Expression via the NF-κb Pathway in Chronic Rhinosinusitis With Nasal Polyps

Deng

Zheng

et al. 2020

Preprint

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Objectives: The hippo-yes-associated protein (YAP) pathway plays an important role in epithelial cell proliferation and inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the underlying mechanisms remain unclear. This study intends to investigate the role of YAP and the nuclear factor kappa-B (NF-κB) signalling pathway in nasal epithelial cell proliferation and the expression of epithelium-derived cytokines in CRSwNP.Methods: The expression levels of YAP, TEAD1, Ki-67, and NF-κB in sinonasal mucosa, primary nasal epithelial cells (NPECs), and human nasal epithelial RPMI 2650 cells were detected by RT-qPCR and immunoblotting. NPECs were cultured and treated with verteporfin (VP), a selective YAP inhibitor, YAP shRNA or BAY 11-7082, a small molecule inhibitor of NF-κB. The relationship between cell proliferation and hippo pathway activity was explored using a cell counting kit-8 (CCK-8) assay, 5(6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) labelling and colony formation assay. The cell cycle and apoptosis were examined through flow cytometry (FCM) assay. The epithelium-derived cytokines including interleukin (IL-) 33, IL-25 and thymic stromal lymphopoietin(TSLP) were detected by RT-qPCR.Results: The hippo pathway effector YAP, Ki-67, p65 NF-κB, and cyclin D1were significantly increased in CRSwNP compared with control mucosa; which was accompanied by overexpression of interleukin (IL)-33, IL-25, and thymic stromal lymphopoieth (TSLP). Pharmaceutical inhibition of YAP by VP suppressed cell proliferation of RPMI 2650 cells by blocking cell cycle progression at G0/G1 without inducing obvious cell apoptosis. Furthermore, lentiviral transfection-mediated knockdown of hippo pathway activity reduced the expression of IL-33,,IL-25, TSLP as well as p65 NF-κB in RPMI 2650 cells. Downregulation of NF-κB pathway with BAY 11-7082 in NPECs could decrease the mRNA level of TSLP, IL-33 and IL-25 accordingly.Conclusions: Inhibition of hippo pathway suppressednasal epithelial cell proliferation and declined the expression of epithelium-derived cytokines IL-33 and IL-25 and TSLP expression via the NF-κB signalling pathway in NPECs.

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Tc17/IL-17A Up-Regulated the Expression of MMP-9 via NF-κB Pathway in Nasal Epithelial Cells of Patients With Chronic Rhinosinusitis

Cited by 47 publications

References 67 publications

Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases

Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases

IL-19 Induced by IL-13/IL-17A in the Nasal Epithelium of Patients with Chronic Rhinosinusitis Upregulates MMP-9 Expression via ERK/NF-kB Signaling Pathway

Yap Promotes Epithelial Cell Proliferation and Epithelium-derived Innate Cytokine Expression via the NF-κb Pathway in Chronic Rhinosinusitis With Nasal Polyps

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