Pirfenidone attenuates IL-1β-induced COX-2 and PGE2 production in orbital fibroblasts through suppression of NF-κB activity

Choi, Youn Hee; Back, Keum Ok; Kim, Hee Ja; Lee, Sang Yeul; Kook, Koung Hoon

doi:10.1016/j.exer.2013.05.001

Cited by 23 publications

(21 citation statements)

References 33 publications

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“…Subsequently, NF-κB translocates to the nucleus, where it binds to regulatory elements within the promoter region of target genes. There is evidence that NF-κB was downstream of COX-2 [38], nevertheless, studies have indicated that the down-regulation of COX-2 expression could inhibit NF-κB [39], [40]. In the present study, we found that sinomenine and celecoxib suppressed the activation of NF-κB pathway in MDR-Caco-2 cells (Fig.…”

Section: Discussionsupporting

confidence: 40%

Sinomenine Sensitizes Multidrug-Resistant Colon Cancer Cells (Caco-2) to Doxorubicin by Downregulation of MDR-1 Expression

et al. 2014

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Chemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance.

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Section: Discussionsupporting

confidence: 40%

Sinomenine Sensitizes Multidrug-Resistant Colon Cancer Cells (Caco-2) to Doxorubicin by Downregulation of MDR-1 Expression

et al. 2014

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“…In human umbilical vein endothelial cells, IL-1b induces HAS2 transcription via the nuclear factor (NF)-jBdependent pathway. 34 Taken together with our previous report of the inhibitory effect of pirfenidone on IL-1b-induced activation of NF-jB signaling pathway in orbital fibroblasts, 19 this pharmacologic action mechanism might be applicable in our present results.…”

Section: Discussionsupporting

confidence: 80%

“…In addition, pirfenidone showed superior potency compared to that of dexamethasone. 16,19 Herein, we revealed an additional effect of pirfenidone at a concentration that is corresponding to the ones used in our previous reports 16,19 : the attenuation of IL-1b-induced HA production through the inhibition of MAPK-mediated HAS expression. However, this inhibitory effect of pirfenidone on MAPK activity, particularly on p38, was relatively incomplete when compared to its effect on HA production.…”

Section: Discussionsupporting

confidence: 53%

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Pirfenidone Attenuates the IL-1β–Induced Hyaluronic Acid Increase in Orbital Fibroblasts From Patients With Thyroid-Associated Ophthalmopathy

Chung

Jeon

Choi

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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“…PFD is known to exert both anti-inflammatory and anti-fibrotic properties via suppressing inflammatory and pro-fibrotic cytokine expression during bleomycin-induced lung fibrosis development [7]. PFD regulates inflammatory cytokine expression through modulating cell signaling, including nuclear factor kappa B(NF-kB) and P38 mitogen-activated protein kinase (MAPK) pathways [8, 9]. Anti-fibrotic mechanisms for PFD have been postulated to be mainly attributed to attenuating protein levels and signaling pathways of pro-fibrotic growth factors, including transforming growth factor (TGF)-β, platelet-derived growth factor (PDGF), and basic-fibroblast growth factor (bFGF) [7, 10, 11].…”

Section: Introductionmentioning

confidence: 99%

Pirfenidone inhibits myofibroblast differentiation and lung fibrosis development during insufficient mitophagy

et al. 2017

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BackgroundPirfenidone (PFD) is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis (IPF), but its precise mechanism of action remains elusive. Accumulation of profibrotic myofibroblasts is a crucial process for fibrotic remodeling in IPF. Recent findings show participation of autophagy/mitophagy, part of the lysosomal degradation machinery, in IPF pathogenesis. Mitophagy has been implicated in myofibroblast differentiation through regulating mitochondrial reactive oxygen species (ROS)-mediated platelet-derived growth factor receptor (PDGFR) activation. In this study, the effect of PFD on autophagy/mitophagy activation in lung fibroblasts (LF) was evaluated, specifically the anti-fibrotic property of PFD for modulation of myofibroblast differentiation during insufficient mitophagy.MethodsTransforming growth factor-β (TGF-β)-induced or ATG5, ATG7, and PARK2 knockdown-mediated myofibroblast differentiation in LF were used for in vitro models. The anti-fibrotic role of PFD was examined in a bleomycin (BLM)-induced lung fibrosis model using PARK2 knockout (KO) mice.ResultsWe found that PFD induced autophagy/mitophagy activation via enhanced PARK2 expression, which was partly involved in the inhibition of myofibroblast differentiation in the presence of TGF-β. PFD inhibited the myofibroblast differentiation induced by PARK2 knockdown by reducing mitochondrial ROS and PDGFR-PI3K-Akt activation. BLM-treated PARK2 KO mice demonstrated augmentation of lung fibrosis and oxidative modifications compared to those of BLM-treated wild type mice, which were efficiently attenuated by PFD.ConclusionsThese results suggest that PFD induces PARK2-mediated mitophagy and also inhibits lung fibrosis development in the setting of insufficient mitophagy, which may at least partly explain the anti-fibrotic mechanisms of PFD for IPF treatment.

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Pirfenidone attenuates IL-1β-induced COX-2 and PGE2 production in orbital fibroblasts through suppression of NF-κB activity

Cited by 23 publications

References 33 publications

Sinomenine Sensitizes Multidrug-Resistant Colon Cancer Cells (Caco-2) to Doxorubicin by Downregulation of MDR-1 Expression

Sinomenine Sensitizes Multidrug-Resistant Colon Cancer Cells (Caco-2) to Doxorubicin by Downregulation of MDR-1 Expression

Pirfenidone Attenuates the IL-1β–Induced Hyaluronic Acid Increase in Orbital Fibroblasts From Patients With Thyroid-Associated Ophthalmopathy

Pirfenidone inhibits myofibroblast differentiation and lung fibrosis development during insufficient mitophagy

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