Elass Elisabeth, Coddeville Bernadette, Kremer Laurent, Mortuaire Marlène, Mazurier Joël, Guérardel Yann
Unité de Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologies de Lille, UMR CNRS 8576, IFR 147, 59655 Villeneuve d'Ascq Cedex, France.
FEBS Lett. 2008 Feb 6;582(3):445-50. doi: 10.1016/j.febslet.2008.01.007. Epub 2008 Jan 15.
Mycobacterial lipomannan (LM) and lipoarabinomannan (LAM) regulate macrophage activation by interacting with Toll-like receptors (TLRs). The intracellular signalling pathways elicited by these complex molecules are poorly defined. We have demonstrated that LM purified from various mycobacterial species, but not LAM from Mycobacterium kansasii or Mycobacterium bovis BCG, induced expression of the MAP kinase phosphatase 1 (MKP-1) in macrophages. Anti-TLR2 antibodies, as well as specific ERK and p38 MAPK inhibitors, decreased MKP-1 transcription in LM-stimulated cells. These findings suggest that the binding of LM to TLR2 triggers MAPK activation, followed by an up-regulation of MKP-1 expression, which in turn may act as a negative regulator of MAPK activation.
分枝杆菌脂甘露聚糖（LM）和脂阿拉伯甘露聚糖（LAM）通过与Toll样受体（TLR）相互作用来调节巨噬细胞的激活。这些复杂分子引发的细胞内信号通路尚不清楚。我们已经证明，从各种分枝杆菌物种中纯化的LM，而不是堪萨斯分枝杆菌或牛分枝杆菌卡介苗的LAM，可诱导巨噬细胞中丝裂原活化蛋白激酶磷酸酶1（MKP-1）的表达。抗TLR2抗体以及特异性ERK和p38丝裂原活化蛋白激酶抑制剂可降低LM刺激细胞中MKP-1的转录。这些发现表明，LM与TLR2的结合触发丝裂原活化蛋白激酶（MAPK）的激活，随后MKP-1表达上调，这反过来可能作为MAPK激活的负调节因子。
