Peptidoglycan induces transcription and secretion of TNF-alpha and activation of lyn, extracellular signal-regulated kinase, and rsk signal transduction proteins in mouse macrophages.
In soluble peptidoglycan (PGN) from staphylococcal cell walls as well as soluble PGN (sPGN) secreted by staphylococci in the presence of beta-lactam antibiotics induced TNF-alpha mRNA and secretion of bioactive TNF-alpha in the murine RAW264.7 macrophage cell line, PGN and sPGN also induced rapid and dose-dependent tyrosine phosphorylation of several cellular proteins, including lyn and mitogen-activated protein kinases (extracellular signal-regulated kinases; but not hck, fgr, or vav) and increased the activities of mitogen-activated protein and rsk kinases. These PGN- and sPGN-induced effects were qualitatively similar to the effects induced by ReLPS, but higher concentrations of PGN and sPGN than ReLPS were required. In contrast to the ReLPS-induced effects, the PGN- and sPGN-induced effects were not inhibited by polymyxin B. All PGN-, sPGN-, and ReLPS-induced effects were serum independent, since they were observed both in RAW264.7 cells grown and stimulated in the presence of serum and in the cells adapted to growth and stimulated in a serum- and albumin-free medium. These results indicate that lyn, extracellular signal-regulated kinase, and rsk signal transduction molecules may be involved in macrophage activation by PGN and further support the idea that PGN and LPS may activate the cells through similar mechanisms.
Gupta
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Northwest Center for Medical Education, Indiana University School of Medicine, Gary 46408, USA.
Jin
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Dziarski
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D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry* / Q000187:drug effects; D051379:Mice; D010457:Peptidoglycan / Q000494:pharmacology*; D011494:Protein Kinases / Q000096:biosynthesis / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019061:src-Family Kinases
D008070:Lipopolysaccharides; D010457:Peptidoglycan; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases