Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LIGHT is a member of the TNF superfamily, which is transiently expressed on the surface of activated T lymphocytes and immature dendritic cells. Its known receptors are herpesvirus entry mediator (HVEM) prominently in T lymphocytes, and lymphtoxin beta receptor (LTbetaR) in stromal cells or nonlymphoid hematopoietic cells. Previous studies have shown that overexpression of LIGHT on T cells could lead to autoimmune reaction including lymphocytes activation, inflammation, and tissue destruction. To address the role of LIGHT/HVEM signaling in autoimmune hepatitis, an experimental colitis model induced by intravenous administration of concanavalin A (ConA) was given a soluble LTbetaR-Ig fusion protein as a competitive inhibitor of LIGHT/HVEM pathway. Marked elevation of LIGHT expression was detected in isolate intrahepatic leukocytes (IHLs) of the experimental animal. Treatment with LTbetaR-Ig significantly attenuated the progression and histological manifestations of the hepatic inflammation and reduced the production of inflammatory cytokines including TNF-alpha, IFN-gamma. Moreover, LTbetaR-Ig treatment significantly down-regulated LIGHT expression, leading to reduced lymphocytes (particularly CD4+ T cells), infiltrating into the hepatic inflammation and inhibited NF-kappaB activation and expression. We postulated that blockade of LIGHT/HVEM signaling by LTbetaR-Ig may ameliorate hepatitis by down-regulating LIGHT expression, and therefore we envision that LTbetaR-Ig would prove to a promising strategy for the clinical treatment of human autoimmune hepatitis.
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PMID:Lymphtoxin beta receptor-Ig protects from T-cell-mediated liver injury in mice through blocking LIGHT/HVEM signaling. 1701 45

LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for binding herpesvirus entry mediator on T cells) is a recently identified of the tumor necrosis factor alpha (TNF-alpha) ligand superfamily. We wanted to establish whether the presence of chronic viral hepatitis could be implicated in enhanced inflammation as well as the elevation of plasma LIGHT levels in haemodialyzed (HD) patients. The plasma levels of LIGHT, high sensitivity C-reactive protein (hs CRP) and TNF-alpha were measured in HD patients with hepatitis in comparison to subjects without hepatitis and to healthy volunteers. The values of hs CRP and TNF-alpha were significantly elevated in HD patients when compared to the controls. TNF-alpha levels were significantly higher in the hepatitis-positive relative to the hepatitis-negative group (p <0.01). LIGHT levels were significantly decreased in hepatitis-negative patients as compared to controls (p <0.001) and hepatitis-positive group (p < 0.01). Both LIGHT and TNF-alpha were directly associated with the presence of hepatitis. Multiple stepwise regression analysis identified increased iron levels as the only independent variable significantly associated with increased LIGHT (beta=0.475, p=0.003). These results suggest the presence of chronic viral hepatitis and iron levels are novel determinants of the increased LIGHT in the plasma of HD patients.
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PMID:Chronic viral hepatitis and iron affect the plasma levels of LIGHT--a new member of the TNF superfamily in uraemic haemodialyzed patients. 1782 30

The BTLA-HVEM checkpoint axis plays extensive roles in immunomodulation and diseases, including cancer and autoimmune disorders. However, the functions of this checkpoint axis in hepatitis remain limited. In this study, we explored the regulatory role of the Btla-Hvem axis in a ConA-induced hepatitis model in zebrafish. Results showed that Btla and Hvem were differentially expressed on intrahepatic Cd8+ T cells and hepatocytes. Knockdown of Btla or Hvem significantly promoted hepatic inflammation. Btla was highly expressed in Cd8+ T cells in healthy liver but was downregulated in inflamed liver, as evidenced by a disparate proportion of Cd8+Btla+ and Cd8+Btla- T cells in individuals without or with ConA stimulation. Cd8+Btla+ T cells showed minimal cytotoxicity to hepatocytes, whereas Cd8+Btla- T cells were strongly reactive. The depletion of Cd8+Btla- T cells reduced hepatitis, whereas their transfer enhanced hepatic inflammation. These observations indicate that Btla endowed Cd8+Btla+ T cells with self-tolerance, thereby preventing them from attacking hepatocytes. Btla downregulation deprived this tolerization. Mechanistically, Btla-Hvem interaction contributed to Cd8+Btla+ T cell tolerization, which was impaired by Hvem knockdown but rescued by soluble Hvem protein administration. Notably, Light was markedly upregulated on Cd8+Btla- T cells, accompanied by the transition of Cd8+Btla+Light- to Cd8+Btla-Light+ T cells during hepatitis, which could be modulated by Cd4+ T cells. Light blockade attenuated hepatitis, thereby suggesting the positive role of Light in hepatic inflammation. These findings provide insights into a previously unrecognized Btla-Hvem-Light regulatory network in hepatic homeostasis and inflammation, thus adding a new potential therapeutic intervention for hepatitis.
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PMID:BTLA-HVEM Checkpoint Axis Regulates Hepatic Homeostasis and Inflammation in a ConA-Induced Hepatitis Model in Zebrafish. 3156 9