Indacaterol Inhibits Tumor Cell Invasiveness and MMP-9 Expression by Suppressing IKK/NF-κB Activation

Lee, Su Ui; Ahn, Ki Hoon; Sung, Min Hee; Park, Ji Won; Ryu, Hyung Won; Lee, Hyun Jun; Hong, Sung-Tae; Oh, Sei-Ryang

doi:10.14348/molcells.2014.0076

Cited by 29 publications

(19 citation statements)

References 37 publications

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“…NF-κB transcription binding sites located in human MMP-9 promoter region and revealed that NF-κB is the key point in the upregulation of MMP-9 expression ( 64 ). Consistently, previous studies have shown that MMP-9 is a downstream gene in the NF-κB pathway ( 65 , 66 ). Additionally, NF-κB has been reported as a downstream target of IL-17A signaling pathway ( 39 , 40 ).…”

Section: Discussionsupporting

confidence: 88%

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

Chen

Chang

et al. 2018

Front. Immunol.

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Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the upper airways involving nasal cavity and sinus. Deriving both from its clinical complexity with protean clinical manifestations as well its pathogenetic heterogeneity, the molecular mechanisms contributing to the pathogenesis of CRS remain unclear, and attract a wide interest in the field. Current evidences indicate that IL-17A is highly expressed in chronic rhinosinusitis with nasal polyps (CRSwNP). However, its pathogenetic role in regulation of tissue remodeling of CRSwNP remains unknown. The present study aimed to investigate the cellular origins and functions of IL-17A cytokine in CRSwNP, and further determined whether IL-17A could affect the expression of metalloproteinases (MMPs), the remodeling factors of CRSwNP. The results showed that the expression of IL-17A was upregulated in nasal tissues of patients with CRSwNP compared to those with chronic rhinosinusitis without nasal polyps (CRSsNP) and controls. CD8+ cytotoxic T lymphocytes (Tc) were major IL-17A producers in nasal tissues of CRSwNP. Interleukin (IL)-17-producing CD8+ T cells (Tc17) was significantly higher in nasal tissues of CRSwNP than CRSsNP and controls. Nonetheless, no difference was observed among the IL-17A in peripheral blood lymphocytes of these three groups. Moreover, in the same patients, IL-17A expression was negligible in lymphocytes of peripheral blood when compared with nasal tissues. Increased gene and protein expression of MMP-7 and MMP-9 in patients with CRSwNP compared with controls were observed. In CRSwNP samples, IL-17A receptor (IL-17AR) co-localized with MMP-9 and they were mainly expressed in the epithelial cells. MMP-9 expression was up-regulated both in Primary human nasal epithelial cells (PHNECs) and a nasal epithelial cell line (RPMI 2650) by IL-17A treatment, and diminished by anti-IL-17AR treatment. Furthermore, IL-17A promoted the expression of MMP-9 by activating the NF-κB signal pathway. Thus, our results have revealed a crucial role of IL-17A and Tc cells on pathogenesis and tissue remodeling of CRSwNP.

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Section: Discussionsupporting

confidence: 88%

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

Chen

Chang

et al. 2018

Front. Immunol.

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“…Upon stimulation, this composite is broken down and NF-κB is activated, translocating into the nucleus and controlling transcription of a large number of inflammatory genes (29). As expression of these pro-inflammatory mediators is known to be regulated by NF-κB (30,31), the results of the present study indicated that transcriptional inhibition of these pro-inflammatory mediators by DOME are due to blockage of the NF-κB signaling pathway. In addition, it was demonstrated that translocation of activated NF-κB p65 to the nucleus is significantly inhibited by DOME.…”

Section: Discussionmentioning

confidence: 52%

Dipterocarpus obtusifolius attenuates the effects of lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages

Park

Kwon

et al. 2017

Molecular Medicine Reports

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Dipterocarpus obtusifolius has been traditionally used as a herbal medicine and is considered to have anticancer properties. The biological activity of D. obtusifolius in inflammation and the underlying mechanisms of its activity remain to be elucidated. The present study investigated the effects of D. obtusifolius methanolic extract (DOME) on lipopolysaccharide (LPS)‑stimulated inflammation in RAW264.7 cells. The effects of DOME on the production of nitric oxide, prostaglandin E2 and pro‑inflammatory cytokines were assessed by ELISA, western blot analysis and reverse transcription‑quantitative polymerase chain reaction. It was demonstrated that expression of inducible nitric oxide synthase, cyclooxygenase‑2, interleukin‑1β and tumor necrosis factor‑α was suppressed by DOME in LPS‑stimulated cells. Furthermore, treatment with DOME suppressed phosphorylation of mitogen activated protein kinase (MAPK) molecules, including extracellular signal‑regulated kinase, c‑Jun N‑terminal kinase and p38 MAPK. Translocation of the nuclear factor‑κB p65 subunit into the nucleus was additionally inhibited by DOME. Phosphorylation of MAPK promoter activity was inhibited by treatment with DOME, PD98059, SB202190 and SP600125. These results demonstrated that DOME inhibits LPS‑induced inflammatory responses. Therefore, DOME may be a potential therapeutic approach for the treatment of inflammatory diseases.

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“…It is known that AP-1 and NF-B transcription factors are important for MMP-9 induction by growth factors, cytokines, and PMA in various cell types (Lee et al, 2014;Lianxu et al, 2006;Shin et al, 2002). We found that galangin and kaempferol drastically decrease IB phosphorylation and increase IB levels.…”

Section: Discussionmentioning

confidence: 67%

Galangin and Kaempferol Suppress Phorbol-12-Myristate-13-Acetate-Induced Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma HT-1080 Cells

Choi¹,

Lee²,

Lee³

2015

Molecules and Cells

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Matrix metalloproteinase (MMP)-9 degrades type IV collagen in the basement membrane and plays crucial roles in several pathological implications, including tumorigenesis and inflammation. In this study, we analyzed the effect of flavonols on MMP-9 expression in phorbol-12-myristate-13-acetate (PMA)-induced human fibrosarcoma HT-1080 cells. Galangin and kaempferol efficiently decreased MMP-9 secretion, whereas fisetin only weakly decreased its secretion. Galangin and kaempferol did not affect cell viability at concentrations up to 30 M. Luciferase reporter assays showed that galangin and kaempferol decrease transcription of MMP-9 mRNA. Moreover, galangin and kaempferol strongly reduce IB phosphorylation and significantly decrease JNK phosphorylation. These results indicate that galangin and kaempferol suppress PMA-induced MMP-9 expression by blocking activation of NF-B and AP-1. Therefore, these flavonols could be used as chemopreventive agents to lower the risk of diseases involving MMP-9.

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Indacaterol Inhibits Tumor Cell Invasiveness and MMP-9 Expression by Suppressing IKK/NF-κB Activation

Cited by 29 publications

References 37 publications

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

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

Dipterocarpus obtusifolius attenuates the effects of lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages

Galangin and Kaempferol Suppress Phorbol-12-Myristate-13-Acetate-Induced Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma HT-1080 Cells

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