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 Printable version |
Activation of the lymphotoxin‐beta receptor induces NFκB‐dependent interleukin‐6 and MIP‐2 secretion in mouse fibrosarcoma cells |
European Cytokine Network. Volume 14, Number 2, 103-7, April 2003, Original article
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 Free Article
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Author(s) : Thomas Hehlgans, Peter Mller, Peter Stopfer, and Daniela N. Männel |
Summary : Activation of the lymphotoxin beta‐receptor (LTβR), a member of the tumor necrosis factor receptor family, plays a crucial role in lymphoid organogenesis and tumor development. Lymphotoxin α
1β
2 (LTα
1β
2) and LIGHT have been identified as membrane anchored ligands for the LTβR. While LTβR is expressed on a wide range of cell types e.g. fibroblasts and monocytes, the ligands are expressed only on activated lymphocytes and NK cells. In order to characterize LTβR expression and the biological consequences of LTβR activation rat anti‐mouse LTβR monoclonal antibodies were generated. These antibodies recognized a mouse LTβR‐Ig fusion protein as well as endogenous LTβR on a variety of mouse fibroblast and fibrosarcoma cell lines. Specificity was demonstrated by the lack of binding to LTβR‐deficient embryonic fibrobasts. Competitive binding studies revealed that three different epitopes were recognized by the monoclonal antibodies. Two of the monoclonals activated the LTβR and induced activation of NFκB and secretion of MIP‐2 and IL‐6 in L929 mouse fibroblast cells. MIP‐2 and IL‐6 secretion was NFκB‐dependent because IκB‐transfected cells released significantly reduced amounts of both mediators. |
Keywords : NFκB\; MIP‐2\; IL‐6 |
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