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Employing a comprehensive methodological approach, the aim of our<jats:italic>in vitro<\/jats:italic>study was to elucidate novel molecular and cellular mechanisms of human peripheral blood immune cells mediated by a fungal \u03b2-1\u21923-D-glucan,<jats:italic>i.e<\/jats:italic>. glucan phosphate, in the presence of lipopolysaccharide (LPS) or toxic shock syndrome toxin 1 (TSST-1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Despite an activation of nuclear factor (NF)\u03baB, NFinterleukin(IL)-6 and NFAT similar to LPS or TSST-1, we observed no significant production of IL-1\u03b2, IL-6, tumor necrosis factor \u03b1 or interferon \u03b3 induced by glucan phosphate. Glucan phosphate-treated leukocytes induced a substantial amount of IL-8 (peak at 18 h: 5000 pg\/ml), likely due to binding of NF\u03baB to a consensus site in the IL-8 promoter. An increase in IL-1receptor antagonist(RA) production (peak at 24 h: 12000 pg\/ml) by glucan phosphate-treated cells positively correlated with IL-8 levels. Glucan phosphate induced significant binding to a known NFIL-6 site and a new NFAT site within the IL-1RA promoter, which was confirmed by inhibition experiments. When applied in combination with either LPS or TSST-1 at the same time points, we detected that glucan phosphate elevated the LPS- and the TSST-1-induced DNA binding of NF\u03baB, NFIL-6 and NFAT, leading to a synergistic increase of IL-1RA. Further, glucan phosphate modulated the TSST-1-induced inflammatory response via reduction of IL-1\u03b2 and IL-6. As a consequence, glucan phosphate shifted the TSST-1-induced IL-1\u03b2\/IL-1RA ratio towards an anti-inflammatory phenotype. Subsequently, glucan phosphate decreased the TSST-1-induced, IL-1-dependent production of IL-2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Thus, \u03b2-1\u21923-D-glucans may induce beneficial effects in the presence of pro-inflammatory responses, downstream of receptor binding and signaling by switching a pro- to an anti-inflammatory IL-1RA-mediated reaction. Our results also offer new insights into the complex regulation of the IL-1RA gene, which can be modulated by a \u03b2-1\u21923-D-glucan.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2172-7-5","type":"journal-article","created":{"date-parts":[[2006,4,6]],"date-time":"2006-04-06T13:31:09Z","timestamp":1144330269000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["\u03b2-(1\u21923)-D-glucan modulates DNA binding of nuclear factors \u03baB, AT and IL-6 leading to an anti-inflammatory shift of the IL-1\u03b2\/IL-1 receptor antagonist ratio"],"prefix":"10.1186","volume":"7","author":[{"given":"Juergen","family":"Luhm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Langenkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Hensel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Frohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg M","family":"Brand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Hennig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"Rink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Koritke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Wittkopf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,3,22]]},"reference":[{"key":"90_CR1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1146\/annurev.mi.22.100168.000511","volume":"22","author":"S Bartnicki-Garcia","year":"1968","unstructured":"Bartnicki-Garcia S: Cell wall chemistry, morphogenesis and taxonomy of fungi. 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