Abstracts (complete list) - Wissenschaft Online

Katharina Gropp, Michael Reuter, Gerhard D. Wieland, Christine Skerka, Peter F. Zipfel
Transcription factors EGR-2 and NFkappaB induce chemokine
synthesis in macrophages challenged with the human
pathogenic yeast Candida albicans
Candida albicans is the major human opportunistic fungal pathogen that can cause lifethreatening
systemic infections. Macrophages represent the first cellular level for
recognition of this human pathogenic yeast and recognize yeast cells by Toll Like
Receptors (TLRs) and induce immune response by synthesis of cytokines.
Recently we described that EGRs (early growth response protein) interact with the
nuclear factor NFkappaB and strongly activate cytokine gene expression. To investigate
whether Candida albicans induces in macrophages the EGR and NFkappaB transcription
factors we determined the induction and also the transcriptional function of EGR and
NFkappaB in macrophages triggered by Candida albicans. RT-RNA analysis revealed
strong induction of EGR-2 and NFkappaB in macrophages exposed to the yeast- and
hyphae-form of Candida albicans. However, whereas the yeast-form of Candida albicans
induces the synthesis of pro-inflammatory cytokines like MIP-1alpha and MIP-1beta, the
hyphae-form leads to the induction of anti-inflammatory cytokines like IL-10. The use of
defined signal transduction inhibitors (PD 98059 and BAY 11-7082) showed that the
induction of cytokines MIP-1alpha and MIP-1beta in response to Candida albicans is
transmitted via the ERK- und NFkappaB-pathway. With transfection assays and confocal
microscopy we demonstrate that the synthesis of chemokines MIP-1alpha and MIP-
1beta in macrophages in response to Candida albicans is mediated by synergistic
activity of EGR-2 and NFkappaB.