Differential modulation of the induction of inflammatory mediators by antibiotics in mouse macrophages in response to viable Gram-positive and Gram-negative bacteria.
We have investigated effects of beta-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.
Cui
Wei
W
Department of Basic Medical Science, University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA.
Lei
Mei-Guey
MG
Silverstein
Richard
R
Morrison
David C
DC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001398:Aztreonam / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015378:Imipenem / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D013205:Staphylococcal Protein A / Q000032:analysis / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000900:Anti-Bacterial Agents; D017077:Culture Media, Conditioned; D018836:Inflammation Mediators; D012333:RNA, Messenger; D013205:Staphylococcal Protein A; D014409:Tumor Necrosis Factor-alpha; D015378:Imipenem; D002442:Ceftazidime; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001398:Aztreonam