Abstracts (complete list) - Wissenschaft Online

Barbara Daller, Michaela Jungbeck, Klaus Pfeffer, Daniela N. Männel, Thomas Hehlgans
Neutralization of LIGHT ameliorates DSS-induced intestinal
inflammation
Activation of the lymphotoxin-b receptor (LTbR) is essential for the development,
maturation and maintenance of secondary lymphoid organs. Recent studies identified
LTbR activation as a critical signaling pathway in the gut and highly relevant to
intestinal inflammation. In order to investigate the role of the LTbR ligand LIGHT
(lymphotoxin-like inducible protein that competes with glycoprotein D for binding to
herpesvirus entry mediator on T cells) in the pathology of colitis, we used LIGHTdeficient
mice in a model of acute colitis induced by oral administration of dextran
sulfate sodium (DSS).
LIGHT-deficient mice developed almost no intestinal inflammation according to
histological score, weight loss, and colonic myeloperoxidase activity. Therefore, mouse
anti-mouse LIGHT monoclonal antibodies were generated by immunization of LIGHTdeficient
mice and standard hybridoma techniques. ELISA and Western blot analysis
demonstrated specific binding of the monoclonal antibodies to mouse LIGHT protein.
Furthermore, two of the monoclonal antibodies neutralized mouse LIGHT in vitro and in
vivo. This was demonstrated by a significantly reduced intestinal inflammation of
C57BL/6 mice treated with anti-mouse LIGHT antibodies during the induction of acute
DSS-colitis.
LIGHT serum levels in patients with Crohn´s disease and ulcerative colitis were found to
be significantly elevated. Thus, the present study clearly demonstrates a role for LIGHT
in enhancing intestinal inflammation and also indicates that neutralization of LIGHT
might be beneficial in treatment of acute inflammatory diseases.