An Essential Role for Death Receptor 3 in Experimental Autoimmune Uveoretinitis

Calder, Claudia J.; Wang, Edward Chung Yern

doi:10.3109/09273948.2012.658135

Cited by 13 publications

(6 citation statements)

References 15 publications

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“…These receptors can activate death caspases within seconds of ligand binding, causing an apoptotic demise of the cell within hours (15). Generally, DR3 regulate inflammation and autoimmune diseases: experimental autoimmune uveoretinitis, allergic lung inflammation and inflammatory arthritis (16,17). Cordycepin was used to treated gastric cancer EBV-positive (SNU-791 cell line), without affecting their cell proliferation or cell cycle arrest (18).…”

Section: Introductionmentioning

confidence: 99%

Cordycepin induces apoptosis in SGC-7901 cells through mitochondrial extrinsic phosphorylation of PI3K/Akt by generating ROS

Nasser

Masood

Wei

et al. 2017

International Journal of Oncology

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Medicinal plants are affluent sources of several effectual natural drugs. Among them cordycepin which is extracted from Cordyceps militaris is a hopeful chemotherapy agent due to its extensive anti-inflammatory, anti-proliferative, antioxidant, and antitumor characteristics. This study investigated the efficacy of cordycepin in the context of human gastric cancer SGC‑7901 and searched for the cell death procedure. Cordycepin incorporates mitochondrial-mediated apoptosis in SGC‑7901 cells with the help of regulating mitochondrial extrinsic pathways by inhibition of A3AR and drive activation of DR3, which promote the activation of PI3K/Akt protein expression as well as collapse of mitochondrial membrane potential (MMP). In addition, phosphorylation of PI3K/Akt and DNA damage by cordycepin induced the production of reactive oxygen species (ROS), and mediates SGC‑7901 cell cycle cessation at S phase. Collectively, this study suggests that cordycepin might be effective as a modern chemotherapy drug for gastric cancer.

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Section: Introductionmentioning

confidence: 99%

Cordycepin induces apoptosis in SGC-7901 cells through mitochondrial extrinsic phosphorylation of PI3K/Akt by generating ROS

Nasser

Masood

Wei

et al. 2017

International Journal of Oncology

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“…In recent years, the DR-3/TL1A axis has emerged as a key regulator of inflammation and autoimmunity in its own right, with in vivo studies of transgenic mice deficient for DR-3 or TL1A and those overexpressing TL1A or dominant-negative forms of DR-3 providing compelling evidence for an essential role of the DR-3/ TL1A axis in many models of inflammatory and autoimmune disease (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). In contrast to TNFRI, much of the function of DR-3 has been attributed to its expression on T cells and natural killer T cells and its role in driving the accumulation or maintenance (23) of Teff cell numbers at sites of pathology, irrespective of their lineage.…”

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confidence: 99%

Regulation of Early Cartilage Destruction in Inflammatory Arthritis by Death Receptor 3

Wang

Newton

Hayward

et al. 2014

Arthritis & Rheumatology

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ObjectiveTo investigate the role of death receptor 3 (DR-3) and its ligand tumor necrosis factor–like molecule 1A (TL1A) in the early stages of inflammatory arthritis.MethodsAntigen-induced arthritis (AIA) was generated in C57BL/6 mice deficient in the DR-3 gene (DR3−/−) and their DR3+/+ (wild-type) littermates by priming and intraarticular injection of methylated bovine serum albumin. The joints were sectioned and analyzed histochemically for damage to cartilage and expression of DR3, TL1A, Ly-6G (a marker for neutrophils), the gelatinase matrix metalloproteinase 9 (MMP-9), the aggrecanase ADAMTS-5, and the neutrophil chemoattractant CXCL1. In vitro production of MMP-9 was measured in cultures from fibroblasts, macrophages, and neutrophils following the addition of TL1A and other proinflammatory stimuli.ResultsDR3 expression was up-regulated in the joints of wild-type mice following generation of AIA. DR3−/− mice were protected against cartilage damage compared with wild-type mice, even at early time points prior to the main accumulation of Teff cells in the joint. Early protection against AIA in vivo correlated with reduced levels of MMP-9. In vitro, neutrophils were major producers of MMP-9, while neutrophil numbers were reduced in the joints of DR3−/− mice. However, TL1A neither induced MMP-9 release nor affected the survival of neutrophils. Instead, reduced levels of CXCL1 were observed in the joints of DR3−/− mice.ConclusionDR-3 drives early cartilage destruction in the AIA model of inflammatory arthritis through the release of CXCL1, maximizing neutrophil recruitment to the joint and leading to enhanced local production of cartilage-destroying enzymes.

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“…Uveitis is another extraintestinal manifestation of IBD that has been associated with the TL1A/DR3 pathway. Specifically, experimental murine autoimmune uveoretinitis was dependent on DR3 as DR3 −/− mice are protected from disease development (124). Although a direct association of TL1A/DR3 with the extraintestinal manifestations of IBD has not been established yet, there is indirect evidence that such an association may exist making TL1A/DR3 a possible common denominator of the gut-skin-joint-eye autoimmune inflammation axis.…”

Section: Tl1a/dr3 In the Crossroads Of Systemic Inflammation: Associamentioning

confidence: 99%

TL1A (TNFSF15) and DR3 (TNFRSF25): A Co-stimulatory System of Cytokines With Diverse Functions in Gut Mucosal Immunity

2019

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TL1A and its functional receptor DR3 are members of the TNF/TNFR superfamilies of proteins. Binding of APC-derived TL1A to lymphocytic DR3 provides co-stimulatory signals for activated lymphocytes. DR3 signaling affects the proliferative activity of and cytokine production by effector lymphocytes, but also critically influences the development and suppressive function of regulatory T-cells. DR3 was also found to be highly expressed by innate lymphoid cells (ILCS), which respond to stimulation by TL1A. Several recent studies with transgenic and knockout mice as well as neutralizing or agonistic antibodies for these two proteins, have clearly shown that TL1A/DR3 are important mediators of several chronic immunological disorders, including Inflammatory Bowel Disease (IBD). TL1A and DR3 are abundantly localized at inflamed intestinal areas of patients with IBD and mice with experimental ileitis or colitis and actively participate in the immunological pathways that underlie mucosal homeostasis and intestinal inflammation. DR3 signaling has demonstrated a dichotomous role in mucosal immunity. On the one hand, during acute mucosal injury it exerts protective functions by ameliorating the severity of acute inflammatory responses and facilitating tissue repair. On the other hand, it critically participates in the pro-inflammatory pathways that underlie chronic inflammatory responses, such as those that take place in IBD. These effects are mediated through modulation of the relative mucosal abundance and function of Th1, Th2, Th17, Th9, and Treg lymphocytes, but also of all types of ILCs. Recently, an important role was demonstrated for TL1A/DR3 as potential mediators of intestinal fibrosis that is associated with the presence of gut inflammation. These accumulating data have raised the possibility that TL1A/DR3 pathways may represent a valid therapeutic target for chronic immunological diseases. Nevertheless, applicability of such a therapeutic approach will greatly rely on the net result of TL1A/DR3 manipulation on the various cell populations that will be affected by this approach.

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An Essential Role for Death Receptor 3 in Experimental Autoimmune Uveoretinitis

Cited by 13 publications

References 15 publications

Cordycepin induces apoptosis in SGC-7901 cells through mitochondrial extrinsic phosphorylation of PI3K/Akt by generating ROS

Cordycepin induces apoptosis in SGC-7901 cells through mitochondrial extrinsic phosphorylation of PI3K/Akt by generating ROS

Regulation of Early Cartilage Destruction in Inflammatory Arthritis by Death Receptor 3

TL1A (TNFSF15) and DR3 (TNFRSF25): A Co-stimulatory System of Cytokines With Diverse Functions in Gut Mucosal Immunity

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