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Journal of Endotoxin Research
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Differential modulation of the induction of inflammatory mediators by antibiotics in mouse macrophages in response to viable Gram-positive and Gram-negative bacteria

Wei Cui

Stowers Institute for Medical Research, 10000 East 50 Street, Kansas City, MO 64110, USA

Mei-Guey Lei

Department of Basic Medical Science University of Missouri-Kansas City School of Medicine

Richard Silverstein

Department of Molecular Biology and Biochemistry, Kansas University Medical Center, Kansas City, Kansas, USA

David C. Morrison

Department of Basic Medical Science University of Missouri-Kansas City School of Medicine, morrisondc{at}umkc.edu, Department of Surgery, University of Missouri-Kansas City School of Medicine, ShocK/Trauma Research Center, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA

We have investigated effects of ß-lactam antibiotics on TNF-{alpha}, and iNOS production from mouse peritoneal macrophages following co-culture with Escherichia coli or Staphylococcus aureus bacteria. Ceftazidime and aztreonam enhanced TNF-{alpha} secretion from macrophages stimulated with E. coli; however, imipenem does not alter either the kinetics or magnitude of TNF-{alpha} in E. coli -treated macrophages. Similar treatments with S. aureus co-cultured with macrophages markedly altered profiles of TNF-{alpha} response characterized by apparent early TNF-{alpha} peak relative to untreated S. aureus. All antibiotics increased E. coli-induced iNOS expression as assessed by both mRNA and protein. These same antibiotics significantly reduced S. aureus-induced iNOS levels of RNA. Both ceftazidime and aztreonam enhanced LPS release from E. coli in comparison to low-level LPS release from imipenem-treated bacteria, consistent with observed differences in TNF-{alpha} release. Incubation of all three antibiotics with S. aureus similarly increased levels of the cell wall constituent protein A detected in supernatants at early time points indicating microbial lysis. In parallel, S. aureus culture supernatants from 2-h incubation with antibiotics enhanced TNF-{alpha} release. These results indicate that different cellular mechanisms contribute to antibiotic-mediated regulation of TNF-{alpha} and iNOS secretion in mouse macrophages in response to E. coli versus S. aureus.

Journal of Endotoxin Research, Vol. 9, No. 4, 225-236 (2003)
DOI: 10.1177/09680519030090040301


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