Inhibition of c-Jun N-terminal kinase and nuclear factor κ B pathways mediates fisetin-exerted anti-inflammatory activity in lipopolysccharide-treated RAW264.7 cells

Kim, Sun-Chae; Kang, Sang-Hun; Jeong, Soo‐Jin; Kim, Sun‐Hee; Ko, Hyun Suk; Kim, Sung‐Hoon

doi:10.3109/08923973.2011.648270

Cited by 55 publications

(33 citation statements)

References 47 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous research indicated that fisetin may protect against the progression of inflammatory diseases by limiting interactions between mast cells and activated T cells [14]. Recently, it has been reported that fisetin exerts anti-inflammatory effect by inhibiting c-Jun N-terminal kinase (JNK) and NF-κB pathways in LPSstimulated RAW264.7 macrophage cells [12]. Furthermore, it has been shown that fisetin can inhibit lipopolysaccharide-induced macrophage activation and dendritic cell maturation [15].…”

Section: Introductionmentioning

confidence: 98%

“…1) is a member of flavonoids, and it is commonly found in plants such as smoke trees and various types of fruits and vegetables such as strawberries, grapes, apples, persimmons, onions, and cucumbers. Various in vitro and in vivo studies have shown that fisetin exerts wide pharmacological properties such as anticancer [9], antioxidant [10], and antiinflammation [11][12][13]. Previous research indicated that fisetin may protect against the progression of inflammatory diseases by limiting interactions between mast cells and activated T cells [14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats

et al. 2015

View full text Add to dashboard Cite

Conclusion: In human infection with H7N9 virus, ALI/ARDS was an important cause of its fatal prognosis. The low expression of cIAP2 inhibited its combination with RIPK1, which caused the combination of RIPK1 and RIPK3.Necroptosis was then induced with the recruitment and activation of MLKL, which destructed the airway epithelium cells followed with ALI/ARDS and triggered the deaths of patients. Background and Objective: We investigated the effect of induced pluripotent stem cells (iPSCs) in moderating pulmonary endothelial leakage in endotoxin-induced acute lung injury (ALI). Methods: Male C57BL/6 mice at 8 to 12 weeks of age were studied. Murine iPSCs were delivered through the tail veins of mice 4 hours after intratracheal instillation of lipopolysaccharide (LPS). Lung histopathologi-cal findings, proteins level and proinflammatory cytokines in peripheral blood and bronchoalveolar lavage fluid (BALF), expression of junctional proteins, and regulatory signaling pathways were analyzed after 24 hours. Human umbilical vein endothelial cells (HUVECs) were cultured as a relevant model as cells expressed major junctional proteins to be responsible for maintaining vascular integrity in vivo. Results: iPSCs significantly diminished the histopathological changes of ALI mice compared to treatment with control cells. Proteins leakage, IL-6 and MIP-2 levels in BALF were significantly reduced in iPSC-treated ALI mice. The iPSC therapy restored VE-cadherin expression in the lung of ALI mice. iPSC reduced the permeability of HUVECs monolayer increased by LPS or VEGF. In HUVECs, the iPSCs restored the expression of VE-cadherin in response to LPS or VEGF via reducing Snail expression and phosphorylation of focal adhesion kinase (FAK) in Tyr397 (pFAK-Tyr397). We found conditioned medium of iPSCs (iPSC-CM) contained TIMP-1, an antiangiogenic factor. Pharmacological TIMP-1 inhibition significantly reduced the histopathological benefit and the change of VE-cadherin and pFAK-Tyr397 expression from iPSC-CM in ALI mice. Conclusion: iPSCs attenuate endothelial cell leakage in endotoxin-induced ALI. These effects are mediated, at least in part, by the enhancement of TIMP-1 activity and reduction of FAK/Snail pathway. Background and Aim: Recent studies have showed that progranu-lin (PGRN) plays essential roles in inflammation and apoptosis. We previously found down-regulation of PGRN during acute lung injury (ALI). However, the roles of PGRN and its miRNAs regulatory mechanisms has not been well studied in ALI. This study was to investigate the roles of PGRN-targeting miRNAs and whether PGRN involved in during ALI. Methods: PGRN knockout/overexpression and wild-type mice via locally instilling recombinant adenovirus containing the mouse PGRN gene and the mouse PGRN shRNA, were subjected to lipopolysaccharide for assessing the roles of PGRN in ALI. The bioinformatics method was used to screen potential miRNAs targeting PGRN in ALI, and determined the exact roles of miR-34b-5p and the mechanism involved in ALI through gain-and loss-of-func...

show abstract

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats

et al. 2015

View full text Add to dashboard Cite

show abstract

“…At present, fisetin has shown multiple biological activities including anti-proliferative (7,8), pro-apoptotic (9-13), neuroprotective (14) and anti-oxidative activities (15). Moreover, fisetin has been shown to suppress the proliferation of a wide variety of tumor cell, including prostate cancer (16), liver cancer (17), colon cancer (18) and leukemia (19) cells, and inhibit the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways in various type of cancer cell, such as colon and pancreatic cancer (14,(20)(21)(22)(23)(24). Fisetin was also reported to reduce the invasive and migratory capacity of the A549 human lung cancer cell line via the extracellular signal-regulated kinase (ERK) signaling pathway (25).…”

Section: Introductionmentioning

confidence: 99%

Fisetin inhibits the growth and migration in the A549 human lung cancer cell line via the ERK1/2 pathway

Wang

Huang

2017

Exp Ther Med

View full text Add to dashboard Cite

Abstract. Lung cancer is the most prevalent malignant tumor type in the developed world and the discovery of novel anti-tumor drugs is a research hotspot. Fisetin, a naturally occurring flavonoid, has been reported to have anti-cancer effects in multiple tumor types. The present study found that fisetin inhibited the growth and migration of non-small cell lung cancer in vitro. MTT, wound-healing, cell-matrix adhesion and Transwell assays were performed and demonstrated that fisetin suppressed proliferation, migration, adhesion and invasion, respectively. Flow cytometric analysis indicated that fisetin induced apoptosis in the A549 cell line by decreasing the expression of c-myc, cyclin-D1, cyclooxygenase-2, B cell lymphoma-2, CXC chemokine receptor type 4, cluster of differentiation 44 and metalloproteinase-2/9, increasing the expression of cyclin dependent kinase inhibitor (CDKN) 1A/B, CDKN2D and E-cadherin and increasing the activity of caspase-3/9 via targeting the extracellular signal-regulated kinase signaling pathway. The results provided comprehensive evidence for the anti-tumor effects of fisetin in non-small cell lung cancer in vitro, which may provide a novel approach for clinical treatment.

show abstract

“…However, signaling pathways other than Erk MAPK have also been implicated in fisetin-induced cellular activation. For example, in LPS-stimulated RAW264.7 macrophages, decreased phosphorylation of JNK and IκBα, but not Erk and p38 MAPK was found (13,30). Interestingly, fisetin also attenuates IκBα and p38 MAPK phosphorylation in LPS-stimulated microglia (31).…”

Section: Discussionmentioning

confidence: 98%

Fisetin Inhibits Osteoclastogenesis Through Prevention of RANKL-Induced ROS Production by Nrf2-Mediated Up-regulation of Phase II Antioxidant Enzymes

et al. 2013

View full text Add to dashboard Cite

Abstract. Osteoclasts (OCLs) are multinucleated bone-resorbing cells that are differentiated by stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor. We recently demonstrated that regulation of heme-oxygenase 1 (HO-1), a stress-induced cytoprotective enzyme, also functions in OCL differentiation. In this study, we investigated effects of fisetin, a natural bioactive flavonoid that has been reported to induce HO-1 expression, on the differentiation of macrophages into OCLs. Fisetin inhibited the formation of OCLs in a dose-dependent manner and suppressed the bone-resorbing activity of OCLs. Moreover, fisetin-treated OCLs showed markedly decreased phosphorylation of extracellular signal-regulated kinase, Akt, and Jun N-terminal kinase, but fisetin did not inhibit p38 phosphorylation. Fisetin up-regulated mRNA expression of phase II antioxidant enzymes including HO-1 and interfered with RANKL-mediated reactive oxygen species (ROS) production. Studies with RNA interference showed that suppression of NF-E2-related factor 2 (Nrf2), a key transcription factor for phase II antioxidant enzymes, rescued fisetin-mediated inhibition of OCL differentiation. Furthermore, fisetin significantly decreased RANKL-induced nuclear translocation of cFos and nuclear factor of activated T cells cytoplasmic-1 (NFATc1), which is a transcription factor critical for osteoclastogenic gene regulation. Therefore, fisetin inhibits OCL differentiation through blocking RANKLmediated ROS production by Nrf2-mediated up-regulation of phase II antioxidant enzymes.

show abstract

Inhibition of c-Jun N-terminal kinase and nuclear factor κ B pathways mediates fisetin-exerted anti-inflammatory activity in lipopolysccharide-treated RAW264.7 cells

Cited by 55 publications

References 47 publications

Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats

Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats

Fisetin inhibits the growth and migration in the A549 human lung cancer cell line via the ERK1/2 pathway

Fisetin Inhibits Osteoclastogenesis Through Prevention of RANKL-Induced ROS Production by Nrf2-Mediated Up-regulation of Phase II Antioxidant Enzymes

Contact Info

Product

Resources

About