Prevention of Ocular Inflammation in Endotoxin-Induced Uveitis with Resveratrol by Inhibiting Oxidative Damage and Nuclear Factor–κB Activation

Kubota, Shunsuke; Kurihara, Toshihide; Mochimaru, Hiroshi; Satofuka, Shingo; Noda, Kousuke; Ozawa, Yoko; Oike, Yuichi; Ishida, Susumu; Tsubota, Kazuo

doi:10.1167/iovs.08-2666

Cited by 141 publications

(108 citation statements)

References 45 publications

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“…Mice were evaluated at 3 h (for NF-kB activation), 6 h (for various gene expression) and 24 h (for leukocyte infiltration) after LPS injection, all of which are the established time points for evaluation of pathological parameters in EIU. [26][27][28] Cell Culture Primary human retinal microvascular endothelial cells (retinal microvasucular endothelial cells (HRMECs); Cell Systems, Kirkland, WA, USA), hTERT-RPE (retinal pigment epithelial cells), Y79 and RAW264.7 cells (American Type Culture Collection, Manassas, VA, USA) were purchased. All cell lines were cultured following the manufacturers' instructions.…”

Section: Methodsmentioning

confidence: 99%

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Angiopoietin-like protein 2 mediates endotoxin-induced acute inflammation in the eye

Kanda

Noda

Oike

et al. 2012

Laboratory Investigation

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Angiopoietin-like protein (Angptl) 2 is a key mediator linking obesity to chronic adipose-tissue inflammation and systemic insulin resistance, and increasing evidence has shown that Angptl2 is associated with various chronic inflammatory diseases such as cancer and dermatomyositis; however, it remains unclear that Angptl2 functions in acute inflammation. In this study, we investigate whether Angptl2 has a role in acute inflammation in the eye with endotoxin-induced uveitis (EIU). Angptl2 was widely expressed in the normal mouse retina, while Angptl2^[-/-] mice did not exhibit any changes in retinal cell marker expression and morphological analyses. Treatment with lipopolysaccharide (LPS) stimulated retinal Angptl2 mRNA expression in vivo and in vitro. We generated EIU in wild-type (C57BL/6) and Angptl2^[-/-] mice by injecting LPS intraperitoneally. Compared to wild-type animals, Angptl2^[-/-] mice significantly reduced various EIU-associated cellular and molecular parameters including leukocyte adhesion to the retinal vessels and infiltration into the vitreous cavity and retinal mRNA expression levels of monocyte chemotactic protein-1, intercellular adhesion molecule-1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, together with nuclear translocation of nuclear factor (NF)-κB p65 subunit. In vitro, antibody-based inhibition of α5β1 integrin, a receptor for Angptl2, significantly repressed LPS-induced expression of IL-6 and TNF-α, both of which are the major inflammatory cytokines derived from macrophages. The present findings indicate that Angptl2 mediates endotoxin-induced retinal inflammation through the activation of NF-κB signaling pathway and suggest a potential validity of Angptl2 as a new molecular target for the treatment of acute inflammation

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Section: Methodsmentioning

confidence: 99%

“…[26][27][28] Briefly, the chest cavity was opened and a cannula was introduced into the left ventricle under deep anesthesia. After injection of PBS to remove erythrocytes and nonadherent leukocytes, FITCconjugated Con A was perfused.…”

Section: Quantification Of Retinal Adherent Leukocytesmentioning

confidence: 99%

Angiopoietin-like protein 2 mediates endotoxin-induced acute inflammation in the eye

Kanda

Noda

Oike

et al. 2012

Laboratory Investigation

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“…Mammals contain seven homologs of yeast Sir2 (Sirtuins, Sirt1-7), which are categorized by their highly conserved central NAD + -binding and catalytic domain and also by unique additional N-terminal and/or C-terminal sequences of variable length (Haigis and Guarente, 2006;Michan and Sinclair, 2007). Like Sir2, the mammal Sirtuins also play important roles in a variety of biological processes, including metabolism (Rodgers et al, 2005;Lomb et al, 2010), apoptosis (Verdin et al, 2010;Kyrylenko and Baniahmad, 2010), oxidative stress and cytokine responses (Kubota et al, 2009) and further influencing aging (Donmez and Guarente, 2010;Haigis and Sinclair, 2010).…”

Section: Introductionmentioning

confidence: 99%

Effect of breed on the expression of Sirtuins (Sirt1-7) and antioxidant capacity in porcine brain

Ren

Shan

Zhu

et al. 2013

Animal

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Sirtuins, NAD-dependent histone deacetylase (HDAC), are correlated to aging and antioxidant. The aim of this study was to determine breed differences of porcine Sirtuins expression and antioxidant capacity in brain between Jinhua pigs (a fatty breed of China) and Danish Landrace pigs (a leaner breed). Effect of age on Sirtuins' expression was also investigated. At the age of 180 days, the mRNA levels of Sirt1, as well as Sirt2 and Sirt4, in Jinhua pigs were greater, but the mRNA levels of Sirt3, Sirt5, Sirt6, and Sirt7 of Jinhua pigs were lower compared with Danish Landrace pigs. Likewise, at the same BW of 64 kg, the mRNA levels of Sirtuins, except Sirt5 and Sirt7, in Jinhua pigs were greater than Danish Landrace pigs. Meanwhile, Jinhua pigs possessed higher antioxidants activity than Danish Landrace pigs either at the same age or at the same BW. Furthermore, mRNA levels of Sirtuins were decreased with age in brain of the two breeds from 30 to 120 days. The results indicated that Sirtuins expression in brain was different between fatty and lean pigs, and Sirtuins expression may be correlated to antioxidant capacity. In addition, age could down-regulate Siruins expression in porcine brain.

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“…Experimental models of allergic conjunctivitis have been already used with the objective of studying the therapeutic effect of several substances, such as lodoxamide, dissodium cromoglicate, benzodiazepine, nedocromil and cholera toxin (Goldschmidt & Luyckx, 1996;Kubota et al, 2009;Kawata et al, 1996;Calonge et al, 1996;Hoyos et al, 2000;Saito et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

“…These results indicate that the synthetic chalcones studied are effective reducing agents, and are reactive towards stabilizing the OH and DPPH radicals. Recently (Kubota et al, 2009), resveratrol an antioxidant polyphenol as chalcones, was shown to prevent the associated cellular and molecular inflammatory responses by inhibiting oxidative damage and redox-sensitive NF-KB activation, in the model of endotoxin-induced uveitis in mice.…”

Section: Discussionmentioning

confidence: 99%

Chalcones from Myracrodruon urundeuva are efficacious in guinea pig ovalbumin-induced allergic conjunctivitis

Albuquerque¹,

Leal²,

Bandeira³

et al. 2011

Rev. bras. farmacogn.

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Abstract:The objective of the study was to verify the effects of dimeric chalcones (urundeuvines A, B, and C) from Myracrodruon urundeuva Allemão, Anacardiaceae (a Brazilian anti-inflammatory species), on an allergic conjunctivitis model. Male guinea-pigs were sensitized with two intraperitoneal injections of ovalbumin (10 μg dissolved in 0.5 mL saline and emulsified in 0.5 mL Freund's adjuvant), at days 0 and 7. At day 24, the animals were submitted to an ocular instillation (right eyes) with ovalbumin. At the next day, the animals were treated with chalcones (0.5 mg, three times a day for 7 days), 0.1% fluormetalone acetate (0.05 mg, as the reference drug) or saline. After anesthesia of the animals, enucleations of their corneas and conjunctivas were carried out for morphometric and histological analyses, at days 1, 3 and 7. Their radical scavenging activity and action on myeloperoxidase were also determined. We demonstrated that chalcones from M. urundeuva stem barks presented anti-inflammatory and antioxidant effects, and drastically inhibited the MPO activity, pointing them as candidates for the treatment of allergic conjunctivitis and other inflammatory conditions.

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Prevention of Ocular Inflammation in Endotoxin-Induced Uveitis with Resveratrol by Inhibiting Oxidative Damage and Nuclear Factor–κB Activation

Abstract: Resveratrol prevented EIU-associated cellular and molecular inflammatory responses by inhibiting oxidative damage and redox-sensitive NF-kappaB activation.

Cited by 141 publications

References 45 publications

Angiopoietin-like protein 2 mediates endotoxin-induced acute inflammation in the eye

Angiopoietin-like protein 2 mediates endotoxin-induced acute inflammation in the eye

Effect of breed on the expression of Sirtuins (Sirt1-7) and antioxidant capacity in porcine brain

Chalcones from Myracrodruon urundeuva are efficacious in guinea pig ovalbumin-induced allergic conjunctivitis

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