Protein phosphorylation pathways involved during lipopolysaccharide-induced expression of CD14 in mouse bone marrow

T Pedron1, R Girard, R Chaby

  • 1Molecular Immunophysiology Unit, URA-1961, National Center for Scientific Research, Pasteur Institute, Paris, France.

Insights

Lipopolysaccharide (LPS) triggers CD14 expression in mouse bone marrow granulocytes via a novel kinase pathway. This response involves protein tyrosine kinase and p38 MAP kinase, but not conventional kinases, suggesting unique signaling mechanisms.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Gram-negative bacteria possess lipopolysaccharide (LPS), a potent immune stimulant.
  • CD14 is a key receptor for LPS, mediating inflammatory responses.
  • Mouse bone marrow granulocytes (BMC) express CD14 upon LPS stimulation, termed inducible LPS receptor (iLpsR).

Purpose of the Study:

  • To elucidate the intracellular signaling pathways involved in LPS-induced CD14 expression in BMC.
  • To identify the specific kinases required for iLpsR expression.

Main Methods:

  • Treatment of BMC with LPS.
  • Inhibition of specific kinase pathways using chemical inhibitors (e.g., PD-98059, K-252a, H-7, KT-5823).
  • Assessment of CD14 expression levels.

Main Results:

  • LPS-induced iLpsR expression in BMC requires protein tyrosine kinase and p38 MAP kinase activation.
  • The ERK pathway is also implicated in this response.
  • Conventional kinases like protein kinase C, myosin light chain kinase, and Ca(2+)/calmodulin-dependent kinases are not essential for iLpsR expression.
  • Inhibition of certain serine/threonine protein kinases significantly reduced BMC response to LPS.

Conclusions:

  • The signaling pathway for LPS-induced CD14 expression in BMC is atypical, involving novel kinase requirements.
  • This atypical signaling may stem from a unique LPS receptor complex or specific CD14 biosynthesis events in BMC.

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