Catechins Inhibit CCL20 Production in IL-17A-Stimulated Human Gingival Fibroblasts

Hosokawa, Yoshitaka; Hosokawa, Ikuko; Ozaki, Kazumi; Nakanishi, Tadashi; Nakae, Hajime; Matsuo, Takashi

doi:10.1159/000257431

Cited by 30 publications

(29 citation statements)

References 24 publications

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“…We observed that TNF-a-induced CCL20 production was dependent on STAT3, p38 and ERK. In line with this, IL-17-induced CCL20 was shown to be dependent on ERK activity in primary human tracheal cells [18], on both ERK and p38 activity in human gingival fibroblasts [19], and on phosphorylation of STAT3 in naïve T-lymphocytes [29]. ERK and p38 phosphorylation have previously been shown to be inhibited by glucocorticoids [30], while glucocorticoids induce IL-10 in a STAT3-dependent way in B-lymphocytes [31].…”

Section: Discussionsupporting

confidence: 61%

“…Since the STAT3, ERK and p38 pathways have been implicated in CCL20 transcription as well as in glucocorticoid-insensitive airway inflammation [18][19][20], we tested the effect of their specific inhibitors on the TNF-a-and budesonide-induced CCL20 production in 16HBE cells. Pre-incubation with the inhibitors of the ERK (U0126), p38 (SB203580) and STAT3 (S3I-201) pathways significantly reduced the TNF-a-induced CCL20 production, indicating a role for these signalling molecules in CCL20 production ( fig.…”

Section: Mechanisms Of Glucocorticoid-induced Ccl20 Secretion In 16hbmentioning

confidence: 99%

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Glucocorticoids induce the production of the chemoattractant CCL20 in airway epithelium

et al. 2014

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Th17-mediated neutrophilic airway inflammation has been implicated in decreased response to glucocorticoids in asthma. We aimed to investigate the effect of glucocorticoids on the airway epithelial release of the neutrophilic and Th17-cell chemoattractant CCL20.We studied CCL20 and CXCL8 sputum levels in asthmatic subjects using inhaled glucocorticoids or not, and the effect of budesonide on CCL20 and CXCL8 production in primary bronchial epithelial cells. The mechanism behind the effect of budesonide-induced CCL20 production was studied in 16HBE14o-cells using inhibitors for the glucocorticoid receptor, intracellular pathways and metalloproteases.We observed higher levels of CCL20, but not CXCL8, in the sputum of asthmatics who used inhaled glucocorticoids. CCL20 levels correlated with inhaled glucocorticoid dose and sputum neutrophils. Budesonide increased tumour necrosis factor (TNF)-a-induced CCL20 by primary bronchial epithelium, while CXCL8 was suppressed. In 16HBE14o-cells, similar effects were observed at the CCL20 protein and mRNA levels, indicating transcriptional regulation. Although TNF-a-induced CCL20 release was dependent on the ERK, p38 and STAT3 pathways, the increase by budesonide was not. Inhibition of glucocorticoid receptor or ADAM17 abrogated the budesonide-induced increase in CCL20 levels.We show that glucocorticoids enhance CCL20 production by bronchial epithelium, which may constitute a novel mechanism in Th17-mediated glucocorticoid-insensitive inflammation in asthma. @ERSpublications Glucocorticoids enhance production of CCL20 by airway epithelial cells: a mechanism of inflammation in asthma?

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Section: Discussionsupporting

confidence: 61%

Section: Mechanisms Of Glucocorticoid-induced Ccl20 Secretion In 16hbmentioning

confidence: 99%

Glucocorticoids induce the production of the chemoattractant CCL20 in airway epithelium

et al. 2014

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“…Inhibition of the IL-17R expression with siRNA in HGF cells showed that IL-17F may mediate the cytokine expression via ERK and NF-κB signaling pathways [33]. The chemokine CCL20 played a crucial role in the recruitment of Th17 cells and thus in the CP disease development [34]. While the IL-17A and IL-17F increased CCL20 production in HGF cells also indicated that CCL20 Fig.…”

Section: Discussionmentioning

confidence: 99%

Overexpression and Potential Regulatory Role of IL-17F in Pathogenesis of Chronic Periodontitis

Luo

Wang

Chen³

et al. 2014

Inflammation

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The objective of this study was to investigate the expression level, clinical significance, and possible regulating role of IL-17F in patients of chronic periodontitis. Periodontal local tissues were obtained from chronic periodontitis (CP) and healthy controls (HC) for real-time PCR (RT-PCR) detection with IL-17F and IL-17A messenger RNA (mRNA). Primary human gingival fibroblasts (HGF) were derived from patients receiving crown-lengthening procedures. Efficiency of small interfering RNA (siRNA) of IL-17R to HGF cells were assessed by Western blot and RT-PCR. Recombinant IL-17F and IL-17A were used to stimulate the HGF cells compared with the control group. Aspects of the nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK) signaling pathways were examined by Western blot. Production of pro-inflammatory cytokines induced by IL-17F and IL-17A was detected by RT-PCR. Statistical analysis was analyzed by SPSS software. It showed significantly elevated levels of IL-17F and IL-17A mRNA in CP gingival tissues compared with HC group (P<0.01). Further analysis showed a significant correlation between IL-17F and IL-17A mRNA in CP group (P<0.05), and both cytokines also correlated with the probing depth (P<0.05). Recombinant IL-17F can induce NF-κB phosphor-p65 and ERK phosphorylation of HGF cells similar to that of IL-17A. Interestingly, we found that both IL-17F and IL-17A could promote the important inflammatory cytokines IL-6, CXCL8, and CCL20 production compared with IL-17R siRNA group (P<0.05). This study indicates that IL-17F may be involved in pathogenesis of periodontitis like IL-17A. The role of IL-17F in disease pathogenesis needs to be further investigated.

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“…However, IL-17 does not directly promote the chemotaxis of human neutrophils from peripheral blood [9]; rather, it promotes the release of recruitment factors from the inflamed microenvironment. Recent studies demonstrate that IL-17 induces the production of IL-6, IL-8, Gro-α, G-CSF, and CCL20 in epithelial cells, synovial fibroblasts, colonic myofibroblasts, and airway smooth muscle cells [10][11][12][13][14]. Moreover, the induction of these inflammatory factors promotes recruitment and accumulation of inflammatory cells, such as neutrophils [15].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment

Yuan

Zhang

Zhuang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Interleukin-17 (IL-17) is a major pro-inflammatory cytokine that initiates and maintains inflammation. However, the molecular mechanisms as to how IL-17 influences endothelial cells to promote neutrophil recruitment are not fully understood. Methods: Human endothelial cells (HMECs) were stimulated with IL-17, and investigated for proliferation, migration, and tubule formation activities. Transwell chemotaxis and adhesion assays were performed to assess neutrophil recruitment. Cytokine production was measured by Cytokine Array Chip and ELISA. Western blotting and immunofluorescent analysis were used to detect the phosphorylation and translocation of STAT3. Specific inhibitors, small interfering RNA, and phosphorylation mutants were used to confirm that IL-17 induced STAT3 activation via IL-17RA signaling. Results: Activation of HMECs with IL-17 induced STAT3 phosphorylation and nuclear translocation, which were associated with induction of GRO-α, GM-CSF and IL-8, and neutrophil recruitment. Phosphorylation of STAT3 was identified mainly at the tyrosine in position 705 (Y705), and the Y705F mutants attenuated IL-17-mediated STAT3 activation. Moreover, specific inhibitors, FLLL31, or siRNA silencing of STAT3 attenuated HMECs activation, resulting in inhibition of GRO-α, GM-CSF, IL-8 production, and neutrophil recruitment. Furthermore, phosphorylation of STAT3 was identified as downstream of IL-17RA signaling. Conclusions: IL-17 induced STAT3 activation as a necessary step in endothelial cell activation and neutrophil recruitment.

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Catechins Inhibit CCL20 Production in IL-17A-Stimulated Human Gingival Fibroblasts

Cited by 30 publications

References 24 publications

Glucocorticoids induce the production of the chemoattractant CCL20 in airway epithelium

Glucocorticoids induce the production of the chemoattractant CCL20 in airway epithelium

Overexpression and Potential Regulatory Role of IL-17F in Pathogenesis of Chronic Periodontitis

Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment

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