title: G(AnH)MTetra, a naturally occurring 1,6-anhydro muramyl dipeptide, induces granulocyte colony-stimulating factor expression in human monocytes: a molecular analysis.
abstract: N-Acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D-isoglutam yl-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.
authors.affiliation: Department of Medicine, University of Groningen, The Netherlands.
authors.forename: W H
authors.initials: WH
authors.lastname: Dokter
authors.forename: A J
authors.initials: AJ
authors.lastname: Dijkstra
authors.forename: S B
authors.initials: SB
authors.lastname: Koopmans
authors.forename: A B
authors.initials: AB
authors.lastname: Mulder
authors.forename: B K
authors.initials: BK
authors.lastname: Stulp
authors.forename: M R
authors.initials: MR
authors.lastname: Halie
authors.forename: W
authors.initials: W
authors.lastname: Keck
authors.forename: E
authors.initials: E
authors.lastname: Vellenga
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002467:Cell Nucleus / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D015398:Signal Transduction; D014158:Transcription, Genetic; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C022226:disaccharide tetrapeptide; D011493:Protein Kinase C