کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9015700 1127349 2005 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lymphtoxin β receptor-Ig ameliorates TNBS-induced colitis via blocking LIGHT/HVEM signaling
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Lymphtoxin β receptor-Ig ameliorates TNBS-induced colitis via blocking LIGHT/HVEM signaling
چکیده انگلیسی
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 β receptor (LTβR) 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 LTβR-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 LTβR-Ig significantly attenuated the progression and histological manifestations of the colonic inflammation and reduced the production of inflammatory cytokines including TNF-α, IL-1β and IL-8. Moreover, LTβR-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 LTβR-Ig and mesalazine showed that both treatments were equally efficacious. We postulated that blockade of LIGHT/HVEM signaling by LTβR-Ig may ameliorate TNBS-induced colitis by down-regulating LIGHT expression, and therefore we envision that LTβR-Ig would prove to a promising strategy for the clinical treatment of inflammatory bowel disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Research - Volume 52, Issue 3, September 2005, Pages 234-244
نویسندگان
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