LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro‐inflammatory cytokines and MMP‐9 in macrophages

Kim, Wonjung; Kang, Younhee; Koh, Eun‐Mi; Ahn, Kwang‐Soon; Cha, Hoon‐Suk; Lee, Won‐Ha

doi:10.1111/j.1365-2567.2004.02004.x

Cited by 62 publications

(61 citation statements)

References 38 publications

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“…LIGHT is up-regulated in the joints of patients with rheumatoid arthritis and mediates proinflammatory effects on joint-resident cells as macrophages (32) and fibroblasts (33). The rational for blocking LIGHT in mice with established joint inflammation was to investigate a phase of the disease in which adaptive immune responses are of minor importance, and to test whether the disease is still influenced.…”

Section: Discussionmentioning

confidence: 99%

Herpesvirus Entry Mediator-Ig Treatment during Immunization Aggravates Rheumatoid Arthritis in the Collagen-Induced Arthritis Model

Pierer¹,

Schulz²,

Rossol³

et al. 2009

The Journal of Immunology

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Section: Discussionmentioning

confidence: 99%

Herpesvirus Entry Mediator-Ig Treatment during Immunization Aggravates Rheumatoid Arthritis in the Collagen-Induced Arthritis Model

Pierer¹,

Schulz²,

Rossol³

et al. 2009

The Journal of Immunology

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“…Although it has been shown in vitro that LIGHT induces apoptosis in several tumor cell lines, there are conflicting reports in regard to the specific receptor mediating this effect (9,10). Recent studies have suggested a potential role of LIGHT in inflammatory diseases including atherosclerosis (11), arthritis (12), IgA nephropathy (13), and inflammatory bowel disease (14). Despite these lines of investigation, the mechanism by which LIGHT mediates inflammatory responses remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Essential role of TNF family molecule LIGHT as a cytokine in the pathogenesis of hepatitis

Anand

Wang

Yoshimura

et al. 2006

Journal of Clinical Investigation

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LIGHT is an important costimulatory molecule for T cell immunity. Recent studies have further implicated its role in innate immunity and inflammatory diseases, but its cellular and molecular mechanisms remain elusive. We report here that LIGHT is upregulated and functions as a proinflammatory cytokine in 2 independent experimental hepatitis models, induced by concanavalin A and Listeria monocytogenes. Molecular mutagenesis studies suggest that soluble LIGHT protein produced by cleavage from the cell membrane plays an important role in this effect through the interaction with the lymphotoxin-β receptor (LTβR) but not herpes virus entry mediator. NK1.1 + T cells contribute to the production, but not the cleavage or effector functions, of soluble LIGHT. Importantly, treatment with a mAb that specifically interferes with the LIGHT-LTβR interaction protects mice from lethal hepatitis. Our studies thus identify a what we believe to be a novel function of soluble LIGHT in vivo and offer a potential target for therapeutic interventions in hepatic inflammatory diseases.

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“…10 LIGHT is produced by activated T cells, monocytes, granulocytes, and immature dendritic cells, and studies in animal models indicate that this cytokine may be crucial for the development of various autoimmune disorders (eg, inflammatory bowel disease, nephritis, and rheumatoid arthritis) through effects on T cells and T-cell homing into inflamed tissues. [11][12][13] Moreover, LIGHT has also been suggested to promote atherogenesis at least partly by inducing matrix metalloproteinase (MMP) activity in macrophages. 14 Because of the expression of certain TNF superfamily members by activated platelets, we investigated whether LIGHT is associated with platelets, and herein we show that these cells express LIGHT and that on activation they release significant amounts of this cytokine.…”

mentioning

confidence: 99%

Platelet-derived LIGHT induces inflammatory responses in endothelial cells and monocytes

Otterdal

Smith

Øie

et al. 2006

Blood

113

115

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Traditionally, platelets are known to play an important role in hemostasis, thrombosis, and wound healing, but increasing evidence suggests that activated platelets also may promote inflammation. Platelet-induced modulation of inflammation seems to involve platelet expression of ligands in the tumor necrosis factor (TNF) superfamily such as CD40 ligand and Fas ligand. The present study demonstrates that LIGHT, another member of the TNF superfamily, is associated with platelets and is released as a soluble ligand on platelet activation. The release of LIGHT involves GP IIb/IIIa-dependent mechanisms and action of metal-dependent proteases as well as intracellular processes such as actin polymerization. We also report that platelet-derived LIGHT is biologically active and can induce an inflammatory response in monocytes and particularly within endothelial cells measured as up-regulation of adhesion molecules and release of chemokines. Moreover, we demonstrate that thrombus material, obtained at the site of plaque rupture in patients with acute myocardial infarction, contains platelet-associated LIGHT, suggesting that LIGHT-mediated inflammation also is operating in vivo within an inflamed and thrombotic vessel wall. The data may suggest a pathogenic role for platelet-derived LIGHT in atherogenesis and plaque destabilization as well as in other inflammatory disorders involving leukocyte infiltration into the vessel wall. IntroductionThe traditional role of platelets as mediators of hemostasis and thrombosis is well documented. Increasing evidence suggests that activated platelets also play a key role in inflammation. Hence, on activation platelets release and express inflammatory mediators, induce an inflammatory response in adjacent leukocytes and endothelial cells, and respond with activation to several of the mediators produced by these cells. [1][2][3][4][5][6] Such interactions between platelets and leukocytes/endothelial cells seem to play a pathogenic role in atherosclerosis as well as in other immune-mediated disorders.Several platelet-derived mediators, such as chemokines and prostaglandins, appear to be involved in platelet-mediated inflammation. 1 Recently, much attention has been focused on the role of platelet-associated CD40 ligand (CD40L), a ligand in the tumor necrosis factor (TNF) superfamily, in this inflammatory loop between platelets and other cells. Thus, platelet-associated CD40L may interact with CD40, which is constitutively expressed on a wide range of cells, such as macrophages, endothelial cells, and vascular smooth muscle cells, resulting in various inflammatory responses. 7,8 Moreover, platelet-derived FasL, another member of the TNF superfamily, was recently shown to induce apoptosis in Fas ϩ tumor cells, further suggesting a role for ligands of this cytokine superfamily in platelet-mediated immune responses. 9 LIGHT, the name of which is derived from "homologous to lymphotoxins, exhibits inducible expression, and competes with herpes simplex virus (HSV) glycoprotein D for herpes virus...

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LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro‐inflammatory cytokines and MMP‐9 in macrophages

Cited by 62 publications

References 38 publications

Herpesvirus Entry Mediator-Ig Treatment during Immunization Aggravates Rheumatoid Arthritis in the Collagen-Induced Arthritis Model

Herpesvirus Entry Mediator-Ig Treatment during Immunization Aggravates Rheumatoid Arthritis in the Collagen-Induced Arthritis Model

Essential role of TNF family molecule LIGHT as a cytokine in the pathogenesis of hepatitis

Platelet-derived LIGHT induces inflammatory responses in endothelial cells and monocytes

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