Mycobacterial lipomannan induces MAP kinase phosphatase-1 expression in macrophages

FEBS Lett. 2008 Feb 6;582(3):445-50. doi: 10.1016/j.febslet.2008.01.007. Epub 2008 Jan 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cells, Cultured
  • Dual Specificity Phosphatase 1 / genetics*
  • Dual Specificity Phosphatase 1 / metabolism
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Humans
  • Lipopolysaccharides / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / metabolism*
  • Macrophages / physiology
  • Mannose / chemistry
  • Mannose / metabolism
  • Mycobacterium kansasii / chemistry
  • Phosphatidylinositols / chemistry
  • Phosphatidylinositols / metabolism
  • Protein Binding
  • Signal Transduction / drug effects
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 2 / physiology
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • p38 Mitogen-Activated Protein Kinases / physiology

Substances

  • Lipopolysaccharides
  • Phosphatidylinositols
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • lipoarabinomannan
  • lipomannan
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Dual Specificity Phosphatase 1
  • Mannose