%0 Journal Article
%T ¦Â-(1¡ú3)-D-glucan modulates DNA binding of nuclear factors ¦ÊB, AT and IL-6 leading to an anti-inflammatory shift of the IL-1¦Â/IL-1 receptor antagonist ratio
%A Juergen Luhm
%A Ulrich Langenkamp
%A Jenny Hensel
%A Christoph Frohn
%A Joerg M Brand
%A Holger Hennig
%A Lothar Rink
%A Petra Koritke
%A Nadine Wittkopf
%A David L Williams
%A Antje Mueller
%J BMC Immunology
%D 2006
%I BioMed Central
%R 10.1186/1471-2172-7-5
%X Despite an activation of nuclear factor (NF)¦ÊB, NFinterleukin(IL)-6 and NFAT similar to LPS or TSST-1, we observed no significant production of IL-1¦Â, IL-6, tumor necrosis factor ¦Á or interferon ¦Ã 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¦ÊB 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¦ÊB, 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¦Â and IL-6. As a consequence, glucan phosphate shifted the TSST-1-induced IL-1¦Â/IL-1RA ratio towards an anti-inflammatory phenotype. Subsequently, glucan phosphate decreased the TSST-1-induced, IL-1-dependent production of IL-2.Thus, ¦Â-1¡ú3-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 ¦Â-1¡ú3-D-glucan.¦Â-1¡ú3-D-glucans occur as a principal component of microbial cell walls or can be secreted from both, non-pathogenic and pathogenic fungi such as S. cerevisae and C. albicans [1]. These ¦Â-1¡ú3-D-linked glucose polymers are characterized as a fungal pathogen-associated molecular pattern (PAMP) [2]. The primary cellular recognition of ¦Â-1¡ú3-D-glucans is mediated by several ¦Â-1¡ú3-
%U http://www.biomedcentral.com/1471-2172/7/5