Streptococcal pyrogenic exotoxins A (SpeA) and C (SpeC) stimulate the production of inducible nitric oxide synthase (iNOS) protein in RAW 264.7 macrophages.
Streptococcal pyrogenic exotoxins A (SpeA) and C (SpeC) are members of a family of superantigens produced by group A streptococci that appear to play a key role in the pathogenesis of streptococcal toxic shock syndrome. Since it is known that nitric oxide (NO) and tumor necrosis factor (TNF) are largely responsible for the shock and multiple organ dysfunction of Gram-negative sepsis, we hypothesized that SpeA and/or SpeC could trigger the production of inducible nitric oxide synthase (iNOS) and/or TNF by murine macrophages. We exposed RAW 264.7 macrophages to increasing concentrations of SpeA or SpeC alone and in combination with recombinant murine interferon-gamma (rIFN gamma) for 16-24 h. We found that both SpeA and SpeC triggered iNOS production in the presence of low concentrations of rIFN gamma, while neither provoked iNOS accumulation in the absence of rIFN gamma. Neither SpeA nor SpeC (with or without rIFN gamma) reproducibly induced TNF production by these murine macrophages. These data indicate that two streptococcal exotoxins up-regulate iNOS production by murine macrophages and suggest that nitric oxide production may play an important role in the pathogenesis of streptococcal toxic shock syndrome.
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Department of Pediatrics, University of Tennessee, Memphis, USA.
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D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D002460:Cell Line; D004790:Enzyme Induction / Q000235:genetics; D005098:Exotoxins / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008565:Membrane Proteins; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II; D011749:Pyrogens / Q000302:isolation & purification / Q000494:pharmacology*; D013297:Streptococcus pyogenes / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D001426:Bacterial Proteins; D005098:Exotoxins; D008565:Membrane Proteins; D011749:Pyrogens; C117980:SpeA protein, Streptococcus pyogenes; D014409:Tumor Necrosis Factor-alpha; C027951:erythrogenic toxin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse