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| Content Provider | PubMed Central |
|---|---|
| Author | Zembowicz, A. Vane, J. R. |
| Abstract | Toxic shock syndrome toxin 1 (TSST-1) is a Mr 22,000 protein produced by Staphylococcus aureus. It is thought to be the cause of toxic shock syndrome. We investigated the hypothesis that TSST-1 induces nitric oxide (NO) synthase and that the NO formed may be involved in the pathogenesis of toxic shock syndrome. We used the murine monocyte-macrophage cell line J744.2 that responds to TSST-1 and also expresses NO synthase activity upon immunological stimulation. J774.2 macrophages stimulated with TSST-1 (10-100 nM) generated nitrite, a breakdown product of NO, and induced concentration-dependent elevations of cGMP in the pig kidney epithelial cell line (LLC-PK1). This latter effect was due to the generation of L-arginine-derived NO for it was (i) abolished by oxyhemoglobin (10 microM), a scavenger of NO, or by methylene blue (10 microM), an inhibitor of NO-activated guanylate cyclase; (ii) potentiated by superoxide dismutase (100 units/ml), which prolongs the life of NO; (iii) inhibited by NG-monomethyl-L-arginine (0.3 mM), an inhibitor of NO synthase; (iv) significantly decreased when L-arginine (0.4 mM) in the medium was replaced by D-arginine (0.4 mM). Moreover, TSST-1 (100 nM) enhanced the activity of cytosolic NO synthase in J774.2 cells. Hydrocortisone (1 microM) but not indomethacin (5 micrograms/ml) or salicylic acid (5 micrograms/ml) prevented the generation of NO2- and the increases in cGMP levels in LLC-PK1 cells induced by J774.2 cells stimulated with TSST-1. The effects of hydrocortisone were partially reversed by coincubation with RU 486 (1 microM), an antagonist of glucocorticoid receptors. Thus, TSST-1 and perhaps other exotoxins produced by Gram-positive bacteria induce NO synthase and the increased NO formation may contribute to toxic shock syndrome and possibly to changes in the immune responses that accompany infection. |
| Starting Page | 2051 |
| File Format | |
| ISSN | 10916490 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 89 |
| Language | English |
| Publisher Date | 1992-03-15 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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