Glucocorticoid-mediated anti-inflammatory effect through NFκB is preserved in the absence of Dexras1

Yong, Ji Hyun; Seok, Jo Woon; Yu, Jung Hwan; Choi, Youn Jeong; Song, Su Jin; Kim, Ara; Kim, Hyo Jung; Kim, Jae-Woo

doi:10.1080/19768354.2016.1140676

Cited by 4 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to provide a mechanism by which we can reduce side effects of glucocorticoids, it is also important to investigate whether Dexras1 is involved in anti-inflammatory effects of glucocorticoids. In this regard, our report that glucocorticoid-mediated NF-κB suppression is preserved in the absence of Dexras1 34 might be interesting to note, thus the inhibition of Dexras1 would be a great target for reducing steroid-mediated side effects. Additional future studies should seek to determine the glucocorticoid-mediated effect of adipogenesis in vivo , perhaps by using animals treated with an excess glucocorticoids.…”

Section: Discussionmentioning

confidence: 83%

Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis

Kim

Jiyoung

Seok

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

Glucocorticoids are associated with obesity, but the underlying mechanism by which they function remains poorly understood. Previously, we showed that small G protein Dexras1 is expressed by glucocorticoids and leads to adipocyte differentiation. In this study, we explored the mechanism by which Dexras1 mediates adipogenesis and show a link to the insulin-like growth factor-1 (IGF-1) signaling pathway. Without Dexras1, the activation of MAPK and subsequent phosphorylation of CCAAT/enhancer binding protein β (C/EBPβ) is abolished, thereby inhibiting mitotic clonal expansion and further adipocyte differentiation. Dexras1 translocates to the plasma membrane upon insulin or IGF-1 treatment, for which the unique C-terminal domain (amino acids 223–276) is essential. Dexras1-dependent MAPK activation is selectively involved in the IGF-1 signaling, because another Ras protein, H-ras localized to the plasma membrane independently of insulin treatment. Moreover, neither epidermal growth factor nor other cell types shows Dexras1-dependent MAPK activation, indicating the importance of Dexras1 in IGF-1 signaling in adipogenesis. Dexras1 interacts with Shc and Raf, indicating that Dexras1-induced activation of MAPK is largely dependent on the Shc-Grb2-Raf complex. These results suggest that Dexras1 is a critical mediator of the IGF-1 signal to activate MAPK, linking glucocorticoid signaling to IGF-1 signaling in adipogenesis.

show abstract

Section: Discussionmentioning

confidence: 83%

Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis

Kim

Jiyoung

Seok

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous studies demonstrated that corticosteroids like Dex phosphate contributed to an anti-inflammatory effect through inhibiting the nuclear factor-kappa B (NF-κB) signal pathway. [ 5 , 6 ] However, whether corticosteroids eye drops are proper for infectious keratitis cure remains a controversial topic. [ 7 ] Lu et al proved that dexamethone could inhibit IL-1-induced collagen degradation and decrease stroma scarring.…”

Section: Introductionmentioning

confidence: 99%

Corticosteroids effects on LPS-induced rat inflammatory keratocyte cell model

et al. 2017

View full text Add to dashboard Cite

PurposeCorticosteroids are efficient anti-inflammation treatments. However, there are still arguments on whether it should be used in keratitis. This study was to observe the effect of corticosteroids on keratocytes both in normal condition and inflammation status in vitro.MethodsRat keratocytes were cultured and used for examination. 10 μg/ml lipopolysaccharide (LPS) was used to establish the inflammatory keratocyte cell model, and prednisolone acetate (PA), dexamethasone (Dex) and fluorometholone (Flu) were used as corticosteroids treatments. 5 d-growth curve and cell viabilities were assayed by CCK8, and cell morphologies and migration rate were studied. TNF-α, IL-6 and IL-1β levels were examined by ELISA. Western blotting was used to quantified type VI collagen (Col VI) and matrix metalloproteinase 9 (MMP9) expressions, and immunofluorescence staining assays of Col I and Col VI were carried out.ResultsIn normal condition, proliferation and migration of keratocytes were slightly influenced in PA, Dex and Flu groups. The secretion of Col I and Col VI was suppressed and MMP9 expression increased in corticosteroids groups. But no significant difference was seen in TNF-α, IL-6 and IL-1β expression levels. In inflammatory status, TNF-α, IL-6 and MMP9 levels increased in LPS group, while they significantly decreased in corticosteroids groups. Although keratocytes viabilities and migration were slightly affected in 24 h, no significant differences were seen between LPS group and corticosteroids groups in 5-d proliferation. Col I and Col VI secretion in LPS-keratocytes was maintained with corticosteroids treatments.ConclusionsCorticosteroids showed lightly effects on keratocytes proliferation and migration, but it successfully decreased TNF-α, IL-6 level and maintained the secretion of and Col I and Col VI, while suppressed the expression of MMP9 in LPS-induced keratocytes. PA was suggested to use in early stage of keratitis clinical treatment.

show abstract

“…PPARγ, known as essential modulators, can regulate nuclear factor-κB (NF-κB) activation in anti-inflammation (Yong et al 2016). Several studies have reported that PPARγ can suppress inflammatory expression by direct interaction with NF-κB, p65 and p50 subunits (Ricote & Glass 2007).…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory actions of plant-derived multiple monoclonal antibody CO17-1A × BR55 related with anti-cancer effects in AOM/DSS-induced colorectal cancer mouse via down-regulating of ERK1/2

Kwak

Heo

Kim

et al. 2016

Animal Cells and Systems

View full text Add to dashboard Cite

Plant-derived multiple monoclonal antibody (mAb) CO17-1A × BR55 (mAb P CO17-1A × BR55) produced in transgenic tobacco plants were cross-pollinated with mAb CO17-1A and mAb BR55. Human anti-colorectal cancer multiple mAb CO17-1A × BR55 was cloned using pBI121 vector. Mice were given a single intraperitoneal injection of azoxymethane (AOM) with 10 mg/kg body weight. Starting 1 week after the injection, mice received 2% dextran sulfate sodium (DSS) in the drinking water for 1 week. In addition, the mice were injected intraperitoneal with mAbs dissolved in phosphate buffered saline (100 μg/mouse) twice per week for 4 weeks. Apoptotic cell death, expression of pro-apoptotic proteins, activity of inflammatory cytokines and ERK pathway phosphorylation were assayed by Western blot and TUNEL kit. mAb P CO17-1A × BR55 meaningfully and efficiently suppressed the development of AOM/DSS-induced colorectal inflammation and colorectal tumors, as determined by a reduced activation of inflammatory cytokines, number of colorectal tumor-induced mouse, number of tumor per mouse colon than other mAbs. Cell death by apoptosis was much increased in the mAb P CO17-1A × BR55-treated tumor compared with negative control. Apoptotic cell death and expression of pro-apoptotic proteins including Bax and cleaved caspase-3 were highest in treatment with mAb P CO17-1A × BR55. In addition, mAbP CO17-1A × BR55 was meaningfully decreased the expression of inflammatory cytokines, including COX-2, iNOS, p50 and p65, but the expression of PPARγ was significantly increased compared with AOM/DSS-induced carcinogenesis negative control. Moreover, mAb P CO17-1A × BR55 meaningfully repressed the ERK1/2 phosphorylation in AOM/ DSS-induced colorectal tumors. Therefore, our results suggest that multiple mAb P CO17-1A × BR55 have meaningful effects of anti-inflammation related with the anti-carcinogenesis in AOM/ DSS-induced colorectal tumor by inhibition of ERK1/2 phosphorylation. ARTICLE HISTORY

show abstract

Glucocorticoid-mediated anti-inflammatory effect through NFκB is preserved in the absence of Dexras1

Abstract: View related articlesView Crossmark data Citing articles: 1 View citing articles Glucocorticoid-mediated anti-inflammatory effect through NFκB is preserved in the absence of Dexras1

Cited by 4 publications

References 25 publications

Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis

Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis

Corticosteroids effects on LPS-induced rat inflammatory keratocyte cell model

Anti-inflammatory actions of plant-derived multiple monoclonal antibody CO17-1A × BR55 related with anti-cancer effects in AOM/DSS-induced colorectal cancer mouse via down-regulating of ERK1/2

Contact Info

Product

Resources

About