Mycobacterial lipomannan induces MAP kinase phosphatase-1 expression in macrophages.
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.
Elass
Elisabeth
E
Unité de Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologies de Lille, UMR CNRS 8576, IFR 147, 59655 Villeneuve d'Ascq Cedex, France. elisabeth.elass@univ-lille1.fr
Coddeville
Bernadette
B
Kremer
Laurent
L
Mortuaire
Marlène
M
Mazurier
Joël
J
Guérardel
Yann
Y
D002454:Cell Differentiation; D002478:Cells, Cultured; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D008358:Mannose / Q000737:chemistry / Q000378:metabolism; D019909:Mycobacterium kansasii / Q000737:chemistry; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000378:metabolism / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology
D008070:Lipopolysaccharides; D010716:Phosphatidylinositols; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C050016:lipoarabinomannan; C064351:lipomannan; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1; D008358:Mannose