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Gene expression profiling using DNA microarrays identified a rapid and significant upregulation of several pro- as well as anti-inflammatory mediators, many of which have never been previously described in TSS. In vivo administration of staphylococcal enterotoxin B (SEB) led to an increase in the expression of Th0- (IL-2, 240-fold); Th1- (IFN-\u03b3, 360-fold; IL-12, 8-fold); Th2- (IL-4, 53-fold; IL-5, 4-fold) as well as Th17-type cytokines (IL-21, 19-fold; IL-17, 5-fold). The immunoregulatory cytokines (IL-6, 700-fold; IL-10, 18-fold); CC chemokines (such as CCL 2, 11, 3, 24, 17, 12, 7), CXC chemokines (such as CXCL 1, 2, 5, 11, 10, 19); and several proteases (matrix metalloproteinases 13, 8, 3, and 9) were also upregulated. Serum levels of several of these cytokines\/chemokines were also significantly elevated. Pathway analyses revealed significant modulation in a variety of biochemical and cellular functions, providing molecular insights into the pathogenesis of TSS. Administration of bortezomib, a clinically approved proteasome inhibitor capable of blocking NF-\u03baB pathway, was able to significantly modulate the expression of a variety of genes induced by SEB. Thus, our study showed that TSS is a complex process and emphasized the potential of use of bortezomib in the therapy of superantigen-induced TSS.<\/jats:p>","DOI":"10.1152\/physiolgenomics.90385.2008","type":"journal-article","created":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T01:09:50Z","timestamp":1238548190000},"page":"279-293","source":"Crossref","is-referenced-by-count":15,"title":["Early gene expression changes induced by the bacterial superantigen staphylococcal enterotoxin B and its modulation by a proteasome inhibitor"],"prefix":"10.1152","volume":"37","author":[{"given":"Govindarajan","family":"Rajagopalan","sequence":"first","affiliation":[{"name":"Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashenafi Y.","family":"Tilahun","sequence":"additional","affiliation":[{"name":"Department of Immunology, Mayo Clinic College of Medicine, Rochester, 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