Differential activities of secreted lymphotoxin-alpha3 and membrane lymphotoxin-alpha1beta2 in lymphotoxin-induced inflammation: critical role of TNF receptor 1 signaling.
Differential activities of secreted lymphotoxin-alpha3 and membrane lymphotoxin-alpha1beta2 in lymphotoxin-induced inflammation: critical role of TNF receptor 1 signaling.
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发表时间：
1998
影响因子：
4.4
通讯作者：
R. Sacca;C. Cuff;Werner Lesslauer;N. Ruddle
中科院分区：
文献类型：
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作者：
R. Sacca;C. Cuff;Werner Lesslauer;N. Ruddle
光氧素（LT，LT α，TNF β）是直接TNF家族的成员，该家族还包括TNF-α和光氧素-β（LT β）。LT由活化的淋巴细胞产生，并作为分泌的同源三聚体或包括跨膜蛋白LT β的膜相关异源三聚体发挥功能。分泌的LT α 3可以与两种细胞表面受体TNFR 1和TNFR 2结合，而膜结合的异源三聚体LT α 1 β 2已被证明与不同的受体LT β R相互作用。LT α在胰腺和肾脏中的大鼠胰岛素启动子驱动的光氧蛋白（RIPLT）转基因表达位点诱导炎症。为了确定各种配体及其受体在LT诱导的炎症中的作用，将TNFR 1、TNFR 2或LT β缺陷的小鼠与RIPLT转基因小鼠杂交。我们的研究结果表明，LT α诱导的炎症依赖于LT α 3与TNFR 1的相互作用，TNFR 2没有明显的作用，因为在其缺失的情况下，LT α诱导的炎症在定量和定性上与野生型相似。然而，LT β的缺乏导致肾脏浸润加重，浸润中记忆细胞的比例增加。这些数据显示了通过TNFR 1分泌的LT α 3信号在LT α诱导的炎症中的关键作用，以及膜LT α 1 β 2形式在该炎症过程中的单独和独特的作用。
Lymphotoxin (LT, LT alpha, TNF beta) is a member of the immediate TNF family that also includes TNF-alpha and lymphotoxin-beta (LT beta). LT is produced by activated lymphocytes and functions as either a secreted homotrimer or a membrane-associated heterotrimer that includes the transmembrane protein LT beta. Secreted LT alpha3 can bind to two cell surface receptors, TNFR1 and TNFR2, while the membrane-bound heterotrimer LT alpha1beta2 has been shown to interact with a distinct receptor, LT betaR. LT alpha induces inflammation at the sites of expression of a rat insulin promoter-driven lymphotoxin (RIPLT) transgene in the pancreas and kidney. To determine the role of the various ligands and their receptors in LT-induced inflammation, mice deficient in either TNFR1, TNFR2, or LT beta were crossed to RIPLT-transgenic mice. Our results indicate that LT alpha-induced inflammation is dependent on the interaction of LT alpha3 with TNFR1, and there is no obvious role for TNFR2, since in its absence, LT alpha-induced inflammation is quantitatively and qualitatively similar to that seen in the wild type. However, the absence of LT beta results in accentuated infiltration of the kidney with an increase in the proportion of memory cells in the infiltrate. These data show a crucial role for the secreted LT alpha3 signaling via TNFR1 in LT alpha-induced inflammation, and a separate and distinct role for the membrane LT alpha1beta2 form in this inflammatory process.