Effect of arazyme on the lipopolysaccharide-induced inflammatory response in human endothelial cells

Kim, In Sik; Yang, Eun Ju; Shin, Dong‐Ha; Son, Kwang‐Hee; Park, Ho‐Yong; Lee, Ji‐Sook

doi:10.3892/mmr.2014.2231

Cited by 20 publications

(13 citation statements)

References 21 publications

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“…To determine whether chrysin inhibits inflammation, we performed RT-PCR and Western blotting to evaluate the mRNA and protein expression of adhesion molecules. We used 10 μg/mL LPS, a commonly used concentration for inducing inflammation in endothelial cells [ 16 ]. Treatment of bEnd.3 cells with 10 μg/mL LPS significantly increased the levels of ICAM-1, E-selectin, VCAM-1 mRNA, and protein in a time-dependent manner (4–12 h and 12–24 h, respectively) ( Figure 1 a,d).…”

Section: Resultsmentioning

confidence: 99%

Chrysin Attenuates VCAM-1 Expression and Monocyte Adhesion in Lipopolysaccharide-Stimulated Brain Endothelial Cells by Preventing NF-κB Signaling

Lee

2017

IJMS

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Adhesion of leukocytes to endothelial cells plays an important role in neuroinflammation. Therefore, suppression of the expression of adhesion molecules in brain endothelial cells may inhibit neuroinflammation. Chrysin (5,7-dihydroxyflavone) is a flavonoid component of propolis, blue passion flowers, and fruits. In the present study, we examined the effects of chrysin on lipopolysaccharide (LPS)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) in mouse cerebral vascular endothelial (bEnd.3) cells. In bEnd.3 cells, LPS increased mRNA expression of VCAM-1 in a time-dependent manner, and chrysin significantly decreased LPS-induced mRNA expression of VCAM-1. Chrysin also reduced VCAM-1 protein expression in a concentration-dependent manner. Furthermore, chrysin blocked adhesion of monocytes to bEnd.3 cells exposed to LPS. Nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase, which are all activated by LPS, were significantly inhibited by chrysin. These results indicate that chrysin inhibits the expression of VCAM-1 in brain endothelial cells by inhibiting NF-κB translocation and MAPK signaling, resulting in the attenuation of leukocyte adhesion to endothelial cells. The anti-inflammatory effects of chrysin suggest a possible therapeutic application of this agent to neurodegenerative diseases, such as multiple sclerosis, septic encephalopathy, and allergic encephalomyelitis.

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Section: Resultsmentioning

confidence: 99%

Chrysin Attenuates VCAM-1 Expression and Monocyte Adhesion in Lipopolysaccharide-Stimulated Brain Endothelial Cells by Preventing NF-κB Signaling

Lee

2017

IJMS

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“…In addition, arazyme may aggravate the pathogenesis of allergic diseases. However, we elucidated anti-inflammatory effect of arazyme in keratinocytes and endothelial cells (Kim et al, 2013;Kim et al, 2014b). Arazyme has also been shown to effectively alleviate clinical features of atopic dermatitis in an atopic dermatitis-like mouse model.…”

Section: Discussionmentioning

confidence: 98%

“…Arazyme is a metalloprotease that induces anti-inflammatory responses such as downregulation of cytokine and reactive oxygen species (ROS) production (Kim et al, 2013;Kim et al, 2014b). We recently found arazyme to be a useful drug candidate for treatment of atopic dermatitis (Kim et al, 2014a).…”

Section: Discussionmentioning

confidence: 99%

“…Arazyme ameliorates acute liver injury by increasing expression of SMP30 and anti-oxidant proteins (Park et al, 2008). We recently revealed an anti-inflammatory effect of arazyme in both cells and animal models of atopic dermatitis (Kim et al, 2013;Kim et al, 2014a;Kim et al, 2014b). Arazyme suppresses the release of inflammatory cytokines and enhances the expression of skin barrier proteins, specifically filaggrin.…”

Section: Introductionmentioning

confidence: 99%

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Suppressive Effect of Arazyme on Neutrophil Apoptosis in Normal and Allergic Subjects

Kim¹,

Lee²

2014

BSL

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Arazyme is a metalloprotease secreted by Aranicola proteolyticus that was previously shown to suppress cytokine expression of keratinocytes and endothelial cells and inhibit histopathological features in an atopic dermatitis-like animal model. However, the regulatory effects of arazyme in other allergic diseases have yet to be elucidated. In this study, we investigated whether arazyme is effective against neutrophil apoptosis in allergic diseases such as allergic rhinitis and asthma. Arazyme inhibited neutrophil apoptosis of normal subjects in a dose-dependent manner. However, the antiapoptotic effect of arazyme was reversed by LY294002, an inhibitor of PI3K, AKTi, an inhibitor of Akt, PD98059, an inhibitor of MEK, and BAY-11-7085, an inhibitor of NF-κB. Arazyme induced activation of NF-κB via PI3K/Akt/ERK pathway. The anti-apoptotic effect of arazyme is associated with inhibition of cleavage of caspase 3 and caspase 9. Arazyme inhibited constitutive apoptosis of neutrophil in a dose-dependent manner in allergic subjects, and its mechanism was shown to be associated with PI3K/Akt/ERK/NF-κB. The results presented here improve our understanding of neutrophil apoptosis regulation and will facilitate development of drugs for treatment of allergic diseases.

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“…In addition, TDD also significantly downregulated the production or expression of IL‐6, IL‐1β, MCP‐1 and TNF‐α in LPS‐stimulated EA.hy926 cells in a concentration‐dependent manner. Other studies have reported that ROS also contributed to endothelial adhesion molecule expression and cytokine production . To further validate whether the effect of TDD on the inhibition of inflammation and ROS production in LPS‐stimulated EA.hy926 cells was mediated through HMBOX1, HMBOX1 silencing was conducted.…”

Section: Discussionmentioning

confidence: 99%

5,2′‐dibromo‐2,4′,5′‐trihydroxydiphenylmethanone attenuates LPS‐induced inflammation and ROS production in EA.hy926 cells via HMBOX1 induction

Yuan

Feng

Liu

et al. 2018

J Cellular Molecular Medi

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Inflammation and reactive oxygen species (ROS) are important factors in the pathogenesis of atherosclerosis (AS). 5,2′‐dibromo‐2,4′,5′‐trihydroxydiphenylmethanone (TDD), possess anti‐atherogenic properties; however, its underlying mechanism of action remains unclear. Therefore, we sought to understand the therapeutic molecular mechanism of TDD in inflammatory response and oxidative stress in EA.hy926 cells. Microarray analysis revealed that the expression of homeobox containing 1 (HMBOX1) was dramatically upregulated in TDD‐treated EA.hy926 cells. According to the gene ontology (GO) analysis of microarray data, TDD significantly influenced the response to lipopolysaccharide (LPS); it suppressed the LPS‐induced adhesion of monocytes to EA.hy926 cells. Simultaneously, TDD dose‐dependently inhibited the production or expression of IL‐6, IL‐1β, MCP‐1, TNF‐α, VCAM‐1, ICAM‐1 and E‐selectin as well as ROS in LPS‐stimulated EA.hy926 cells. HMBOX1 knockdown using RNA interference attenuated the anti‐inflammatory and anti‐oxidative effects of TDD. Furthermore, TDD inhibited LPS‐induced NF‐κB and MAPK activation in EA.hy926 cells, but this effect was abolished by HMBOX1 knockdown. Overall, these results demonstrate that TDD activates HMBOX1, which is an inducible protective mechanism that inhibits LPS‐induced inflammation and ROS production in EA.hy926 cells by the subsequent inhibition of redox‐sensitive NF‐κB and MAPK activation. Our study suggested that TDD may be a potential novel agent for treating endothelial cells dysfunction in AS.

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Effect of arazyme on the lipopolysaccharide-induced inflammatory response in human endothelial cells

Cited by 20 publications

References 21 publications

Chrysin Attenuates VCAM-1 Expression and Monocyte Adhesion in Lipopolysaccharide-Stimulated Brain Endothelial Cells by Preventing NF-κB Signaling

Chrysin Attenuates VCAM-1 Expression and Monocyte Adhesion in Lipopolysaccharide-Stimulated Brain Endothelial Cells by Preventing NF-κB Signaling

Suppressive Effect of Arazyme on Neutrophil Apoptosis in Normal and Allergic Subjects

5,2′‐dibromo‐2,4′,5′‐trihydroxydiphenylmethanone attenuates LPS‐induced inflammation and ROS production in EA.hy926 cells via HMBOX1 induction

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