Publications (2)6.09 Total impact
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Article: Lymphtoxin beta receptor-Ig protects from T-cell-mediated liver injury in mice through blocking LIGHT/HVEM signaling.
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ABSTRACT: 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.Biological & Pharmaceutical Bulletin 11/2006; 29(10):2025-30. · 1.66 Impact Factor -
Article: Lymphtoxin beta receptor-Ig ameliorates TNBS-induced colitis via blocking LIGHT/HVEM signaling.
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ABSTRACT: 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 lymphocytes activation, inflammation, and tissue destruction focused on intestinal mucosal tissues. To address the role of LIGHT/HVEM signaling in colonic inflammation, an experimental colitis model induced by rectal administration of trinitrobenzene sulfonic acid (TNBS) was given a soluble LTbetaR-Ig fusion protein as a competitive inhibitor of LIGHT/HVEM pathway. Marked elevation of LIGHT expression was detected in colonic tissue of the experimental colitis. Treatment with LTbetaR-Ig significantly attenuated the progression and histological manifestations of the colonic inflammation and reduced the production of inflammatory cytokines including TNF-alpha, IL-1beta and IL-8. Moreover, LTbetaR-Ig treatment significantly down-regulated LIGHT expression, leading to reduced lymphocytes, particularly CD4+ T cells, infiltrating into the colonic inflammation tissue as shown by histological analysis. In addition, comparison of the therapeutic effects on TNBS-induced colitis between LTbetaR-Ig and mesalazine showed that both treatments were equally efficacious. We postulated that blockade of LIGHT/HVEM signaling by LTbetaR-Ig may ameliorate TNBS-induced colitis by down-regulating LIGHT expression, and therefore we envision that LTbetaR-Ig would prove to a promising strategy for the clinical treatment of inflammatory bowel disease.Pharmacological Research 10/2005; 52(3):234-44. · 4.44 Impact Factor
