LIGHT enhances the bactericidal activity of human monocytes and neutrophils via HVEM

Heo, Sook-Kyoung; Ju, Seong‐A; Lee, Sangchul; Park, Sang-Min; Choe, Suck-Young; Kwon, Byungsuk; Kwon, Byoung S.; Kim, Byung-Sam

doi:10.1189/jlb.1104694

Cited by 65 publications

(90 citation statements)

References 37 publications

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“…Mammalian LIGHT has been shown to be expressed on T cells and immature dendritic cells (24,25) and is instrumental in T cell homeostasis and stimulation of monocyte and neutrophil bactericidal activity via the herpes virus entry mediator receptor (26). The highest constitutive expression of LIGHT in unstimulated rainbow trout was observed in the spleen, PBL, gill, kidney, and intestine (Fig.…”

Section: Light (Tnfsf 14) and 4-1bbl (Tnfsf 9)mentioning

confidence: 95%

Early Diversification of the TNF Superfamily in Teleosts: Genomic Characterization and Expression Analysis

Glenney

Wiens

2007

The Journal of Immunology

108

121

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The TNF superfamily (TNFSF) of proteins are cytokines involved in diverse immunological and developmental pathways. Little is known about their evolution or expression in lower vertebrate species. Bioinformatic searches of Zebrafish, Tetraodon, and Fugu genome and other teleost expressed sequence tag databases identified 44 novel gene sequences containing a TNF homology domain. This work reveals the following: 1) teleosts possess orthologs of BAFF, APRIL, EDA, TWEAK, 4-1BBL, Fas ligand, LIGHT, CD40L, RANKL, and possibly TL1A; 2) the BAFF-APRIL subfamily is enriched by a third member, BALM, unique to fish; 3) orthologs of lymphotoxins ␣ and ␤ were not clearly identified in teleosts and are substituted by a related ligand, TNF-New; 4) as many as four TRAIL-like genes are present in teleosts, as compared with only one in mammals; and 5) T cell activation ligands OX40L, CD27L, CD30L, and GITRL were not identified in any fish species. Finally, we characterize mRNA expression of TNFSF members CD40L, LIGHT, BALM, APRIL, Fas ligand, RANKL, TRAIL-like, and TNF-New in rainbow trout, Oncorhynchus mykiss, immune and nonimmune tissues. In conclusion, we identified a total of 14 distinct TNFSF members in fishes, indicating expansion of this superfamily before the divergence of bony fish and tetrapods, ϳ360 -450 million years ago. Based on these findings, we extend a model of TNFSF evolution and the coemergence of the vertebrate adaptive immune system.

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Section: Light (Tnfsf 14) and 4-1bbl (Tnfsf 9)mentioning

confidence: 95%

Early Diversification of the TNF Superfamily in Teleosts: Genomic Characterization and Expression Analysis

Glenney

Wiens

2007

The Journal of Immunology

108

121

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“…Our findings in experimental HF suggest that this receptor can also be expressed in cardiomyocytes, with particularly high expression in the failing myocardium. LIGHT has been reported to promote several effects relevant to HF, such as production of inflammatory cytokines, matrix degradation, and increased production of reactive oxygen species in leukocytes, endothelial cells, and fibroblasts [13,16,22]; some of these effects seem to involve LIGHT-HVEM interaction. Furthermore, studies in animal models suggest that LIGHT-HVEM interaction may play a major role in inflammatory bowel disease, allograft rejection, and graft-versus-host disease [9].…”

Section: Discussionmentioning

confidence: 99%

Increased expression of LIGHT/TNFSF14 and its receptors in experimental and clinical heart failure☆

Dahl

Gullestad

Fevang

et al. 2008

European J of Heart Fail

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Background: Clinical and experimental studies suggest a pathogenic role for inflammation in chronic heart failure (HF). LIGHT is a member of the tumour necrosis factor superfamily involved in innate and adaptive immune responses. Aims: We sought to investigate a potential pathogenic role of LIGHT in chronic HF. Methods: We used various clinical and experimental approaches including studies in post-infarction HF rats and in vitro studies of endothelial cells and peripheral blood mononuclear cells (PBMC). Results: Our main findings were: (i) LIGHT and its receptors (i.e., HVEM and lymphotoxin-β receptor) were regulated during experimental HF, with strong expression in the infarcted area accompanied by up-regulation of HVEM in cardiomyocytes and endothelial cells also in the non-ischaemic part of the left ventricle. (ii) Patients with chronic HF had significantly increased expression of LIGHT on CD3 + T-cells accompanied by increased expression of HVEM on monocytes and within the failing myocardium. (iii) LIGHT induced interleukin (IL)-6 expression in endothelial cells. In HF patients, but not in healthy controls, such an IL-6-inducing effect was also seen in LIGHT activated PBMC. Conclusion: Our findings in both clinical and experimental HF may suggest a role for LIGHT signalling pathways in the progression of chronic HF involving IL-6-related mechanisms.

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“…In activated monocytes, macrophages and neutrophils, LIGHT led to an increased expression of cytokines, such as IL-8 and TNF-a and matrix metalloproteinases, such as matrix metalloproteinase-9. 22,29,31 In Human umbilical vein endothelial cells, LIGHT induced the secretion of chemokines (IL-8 and GRO) and cell-surface expression of adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1).…”

Section: Discussionmentioning

confidence: 99%

“…Among the multiple biological activities described, LIGHT is known to stimulate the expression and/or secretion of various molecules involved in the inflammatory response. 14,22,29,31 Given this background, we studied the secretion of 21 cytokines by human differentiated adipocytes under different LIGHT concentrations. The results showed that differentiated adipocytes from obese subjects spontaneously released pro-inflammatory cytokines Table 4 Diagram showing the changes of cytokine secretion by human differentiated adipocytes incubated with 0, 10, 100 and 1000 ng ml À1 human LIGHT for 24 h…”

Section: Discussionmentioning

confidence: 99%

LIGHT is associated with hypertriglyceridemia in obese subjects and increased cytokine secretion from cultured human adipocytes

et al. 2009

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Background: LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells) is a member of the tumor necrosis factor (TNF) family, primarily expressed in lymphocytes, which was associated with the induction of pro-inflammatory cytokines and alterations of lipid homeostasis in animal models. We aimed to analyze whether LIGHT has a role in the human obesity-associated inflammatory status. Methods: The association between circulating LIGHT concentrations and clinical variables was studied in 190 subjects with different degrees of obesity and glucose tolerance. The expression and release of 21 different cytokines, and the expression of genes involved in lipid metabolism were also evaluated after stimulation with LIGHT in cultured human differentiated adipocytes. Results: Serum LIGHT concentrations positively associated with body mass index (BMI), fat mass, glycated hemoglobin and fasting triglycerides, and negatively with high-density lipoprotein cholesterol. Circulating LIGHT concentrations were significantly increased in morbidly obese subjects and in patients with type 2 diabetes. LIGHT induced the secretion of several cytokines and upregulated the expression and secretion of interleukin-6 (IL-6), IL-8, Growth Regulated Oncogene (GRO) and monocyte chemotactic protein-1 (MCP-1). These observations were concomitant with the activation of nuclear factor (NF)-kB signalling in human differentiated adipocytes. LIGHT also upregulated the expression and synthesis of its own receptor (herpesvirus entry mediator (HVEM)) and decreased the expression of peroxisome proliferator-activated receptor-g (PPAR-g) and fatty acid synthase. Conclusion: These data suggest that LIGHT may have a role in mediating chronic inflammation and alterations of lipid metabolism in obese subjects.

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LIGHT enhances the bactericidal activity of human monocytes and neutrophils via HVEM

Cited by 65 publications

References 37 publications

Early Diversification of the TNF Superfamily in Teleosts: Genomic Characterization and Expression Analysis

Early Diversification of the TNF Superfamily in Teleosts: Genomic Characterization and Expression Analysis

Increased expression of LIGHT/TNFSF14 and its receptors in experimental and clinical heart failure☆

LIGHT is associated with hypertriglyceridemia in obese subjects and increased cytokine secretion from cultured human adipocytes

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