G(ANH)MTETRA, A NATURALLY-OCCURRING 1,6-ANHYDRO MURAMYL DIPEPTIDE, INDUCES GRANULOCYTE-COLONY-STIMULATING FACTOR EXPRESSION IN HUMAN MONOCYTES - A MOLECULAR ANALYSIS

WHA DOKTER, AJ DIJKSTRA, SB KOOPMANS, AB MULDER, BK STULP, MR HALIE, W KECK, E VELLENGA

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Abstract

N-Acetyiglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D-isoglutamyl-m-diaminopimelyl-D-alanine [G(Anh)MTetra], a naturally occurring breakdown product of peptidoglycan from bacterial cell walls, was studied for its ability to induce granulocyte colony-stimulating factor (G-CSF) mRNA and protein expression in human adherent monocytes. Resting monocytes did not express G-CSF mRNA or secrete G-CSF protein. In contrast, monocytes exposed to G(Anh)MTetra showed a dose-dependent increase in G-CSF mRNA accumulation, which correlates with the secretion of G-CSF protein. Maximal levels of G-CSF mRNA were reached within 2 h of activation. Expression of G-CSF was mediated by an increase in the stability of G-CSF transcripts rather than by an increase in the transcription rate of the G-CSF gene. Experiments with the protein synthesis inhibitor cycloheximide revealed that G(Anh)MTetra-induced G-CSF mRNA expression was independent of new protein synthesis, Furthermore, it was shown that the effect of G(Anh)MTetra was regulated by a protein kinase C-dependent pathway, whereas protein kinase A and tyrosine kinases were not involved. Finally, it was shown that G(Anh)MTetra also induced G-CSF mRNA expression in human endothelial cells. The data indicate that, besides lipopolysaccharide, other naturally occurring bacterial cell wall components are able to induce G-CSF expression in different hematopoietic cells.

Original languageEnglish
Pages (from-to)2953-2957
Number of pages5
JournalInfection and Immunity
Volume62
Issue number7
Publication statusPublished - Jul-1994

Keywords

  • HUMAN-ENDOTHELIAL CELLS
  • PROTEIN KINASE-C
  • SLOW-WAVE SLEEP
  • MESSENGER-RNA
  • ESCHERICHIA-COLI
  • G-CSF
  • HUMAN-URINE
  • PEPTIDOGLYCAN
  • LIPOPOLYSACCHARIDE
  • TRANSGLYCOSYLASE

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