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The Fungicidal Potential of Dimethyloxaglycine (DMOG) in Infected Bone Marrow Macrophages of C57 BL6‐J mice
Author(s) -
Lopez Abdon,
Buesing William,
Tweedle Jamie,
Deep George
Publication year - 2017
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.31.1_supplement.676.6
Subject(s) - bone marrow , immune system , incubation , cytokine , transcription factor , microbiology and biotechnology , biology , immunology , chemistry , gene , biochemistry
Histoplasma capsulatum, a dimorphic fungal pathogen, can be found in all regions of the United States and is the most common pulmonary fungal infection in immune‐depressed patients. HIF‐1 is a heterodimeric transcription factor, composed of Hif‐1βand HIF‐1α, whose expression is regulated by oxygen, and regulates metabolic and immune response genes. Dimethyloxaglycine(DMOG), inhibits hydroxylases and induces HIF‐1‐dependent transcription. AIM To investigate the fungicidal potential of DMOG in infected bone marrow macrophages of C57 BL6‐J mice and its possible mechanism dependence in HIF‐1α. Methods Bone marrow was harvested from HIF‐1α knock‐out and wild type (WT) mice, and then, cultured with GM‐CSF. Bone Marrow macrophages(BMm) were plated in 24, 48 and 96 well‐plates, with 1 × 106, 5 × 105 and 1 × 105 cells per well respectively, and treated 6hrs prior to H.capsulatum infection. BMm were treated with: Medium), Vehicle (DMSO) or 0.1% DMOG. After 24, 48 and 72hrs post infection, supernatant was collected, BMms were lysed, transferred to culture plates, and fungal burden was counted after a week of incubation at 29°C. Cytokine levels were measured by ELISA, and PCR. Results In the 48 well plates, WT‐BMm treated with DMOG had a higher tendency of fungal clearance. A high expression of IL‐1β and a low expression of GM‐CSF at the protein level was observed in this group. At the transcriptional level, we saw an increase of TGF‐β. Conclusion DMOG enhances H. capsulatum clearance by macrophages, through a mechanism that may stabilize HIF‐1α and induces changes in cytokines expression.