title: Fungal cell wall agents suppress the innate inflammatory cytokine responses of human peripheral blood mononuclear cells challenged with lipopolysaccharide in vitro.
abstract: Exposure to high levels of fungi might lead to diseases, such as airway inflammation, hypersensitivity pneumonitis and allergy. To comprehend the mechanisms behind the exposure to fungi and a disease, we examined the in vitro innate inflammatory cytokine response of human peripheral blood mononuclear cells (PBMC) challenged by fungal cell wall agents (FCWAs), i.e., soluble and particulate (1→3)-β-D-glucan-curdlan (BGS and BGP), zymosan (ZYM) and chitosan (CHT) in the absence or presence of lipopolysaccharide (LPS). We also studied FCWA effects on the mRNA expression of dectin-1, TLR2, TLR4 and mannose receptor (MR) by real-time RT-PCR. Our results demonstrated that BGP strongly induced the secretion of TNF-α, IL-6, IL-10 and IL-12; BGS, ZYM and CHT were weaker, but still significant cytokine inducers. We showed that BGS significantly augmented the LPS-induced in vitro secretion of TNF-α. On the other hand, BGP, ZYM and CHT suppressed the LPS-induced production of all cytokines. At the mRNA level, the dectin-1, TLR2 and TLR4 expressions were significantly reduced by all FCWAs in the absence of LPS and even more in the presence of LPS. While we demonstrated that the innate inflammatory cytokine response of PBMC induced by CHT was mediated by MR, the MR mRNA expression was significantly reduced by CHT. On the contrary, BGS significantly enhanced the MR mRNA expression. In conclusion, a long-term and massive exposure to LPS and FCWA (e.g., organic dust) may cause an important disruption of normal immune response and allow development and/or persistence of various immunopathological events.
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia. sanja.stopinsek@mf.uni-lj.si
authors.forename: Sanja
authors.initials: S
authors.lastname: Stopinšek
authors.forename: Alojz
authors.initials: A
authors.lastname: Ihan
authors.forename: Branka
authors.initials: B
authors.lastname: Wraber
authors.forename: Marjeta
authors.initials: M
authors.lastname: Terčelj
authors.forename: Barbara
authors.initials: B
authors.lastname: Salobir
authors.forename: Ragnar
authors.initials: R
authors.lastname: Rylander
authors.forename: Saša
authors.initials: S
authors.lastname: Simčič
mesh_terms: D000328:Adult; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005658:Fungi / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000099181:Dectin-1; C495345:TLR4 protein, human