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Inflammatory gene expression in BMDM macrophages in response to fungal metabolites.
Author(s) -
Stallworth Akida,
Osei-Bonsu Daniel,
AZIM ANSER C
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.698.13
Subject(s) - lipopolysaccharide , biology , tumor necrosis factor alpha , pattern recognition receptor , chemokine , transcription factor , nitric oxide synthase , receptor , immunology , microbiology and biotechnology , nitric oxide , signal transduction , chemistry , immune system , innate immune system , gene , biochemistry , endocrinology
PU.1, a member of the Ets family of transcription factors, is a requirement for the proper differentiation of hematopoietic cells during developmental stages. Toll like receptors, a member of the family of pattern recognition receptors (PRRs) bind and recognize LPS triggering a signaling cascade with known activation of the NF‐kappa B canonical pathway to regulate genes involved in microbial clearance. Of the thirteen human TLRs, TLR 2 and TLR 4 have also been shown to recognize both bacteria and fungi and generate a inflammatory response producing COX‐2 and nitric oxide and a variety of cytokines and chemokines including IL‐1 and TNF‐α. Recently we have shown its activation in response to lipopolysaccharide bacterial endotoxin (LPS) in the regulation of pro‐inflammatory gene expression like cyclooxygenase 2. Aspergillus niger and Penicillium notatum both opportunistic fungi, have been shown to have clinical pathologies in immunocomprimised patients which enter the host through spore inhalation. We hypothesize that the fungal metabolites from Aspergillus niger and Penicillium notatum bind and signal through TLR 2 and TLR 4 in both the Raw 264.7 and bone marrow derived macrophage (BMDM) cell which leads to a two fold up‐regulation of COX‐2 protein, nitric oxide synthase (NOS), and tumor necrosis factor alpha (TNF‐α). In addition we believe that there is a link between the expression of these pro‐inflammatory mediators involving transcription factor PU.1, whose regulation is controlled by NIK, in response to the fungal metabolites as has been shown previously in response to LPS from our earlier work.