{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:18:37Z","timestamp":1781108317222,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1992,3,15]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1073\/pnas.89.6.2051","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:18:24Z","timestamp":1149063504000},"page":"2051-2055","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":48,"title":["Induction of nitric oxide synthase activity by toxic shock syndrome toxin 1 in a macrophage-monocyte cell line."],"prefix":"10.1073","volume":"89","author":[{"given":"A","family":"Zembowicz","sequence":"first","affiliation":[{"name":"William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, England."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J R","family":"Vane","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, England."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1992,3,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.89.6.2051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:39:16Z","timestamp":1649857156000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.89.6.2051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,3,15]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1992,3,15]]}},"alternative-id":["10.1073\/pnas.89.6.2051"],"URL":"https:\/\/doi.org\/10.1073\/pnas.89.6.2051","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,3,15]]},"assertion":[{"value":"1992-03-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}