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Determining the Effects of Chronic Interferon Stimulation on Heme Oxygenase‐1 in Human Monocyte Derived Macrophages
Author(s) -
Cobo Bryan,
Garza Rolando,
Kolson Dennis L.
Publication year - 2018
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.2018.32.1_supplement.805.9
Subject(s) - stimulation , heme oxygenase , neurotoxicity , interferon , monocyte , biology , western blot , downregulation and upregulation , microbiology and biotechnology , immunology , heme , medicine , endocrinology , gene , biochemistry , toxicity , enzyme
HIV‐associated neurocognitive disorders (HAND) affect ~40% of the HIV infected population even with the use of combined antiretroviral therapy (cART). We previously reported that the critical cytoprotective enzyme, Heme oxygenase‐1 (HO‐1) is reduced in the brains of HIV infected individuals and that this reduction correlates with increased expression of type 1 interferon response genes and markers of monocyte activation. Furthermore, reduction of HO‐1 protein expression is accompanied by increased HO‐1 RNA expression. We also showed that chronic type 2 interferon (IFN) stimulation in astrocytes leads to HO‐1 protein degradation via an immunoproteasome mediated mechanism. Here, we aim to determine the effects of chronic type 1 and type 2 IFN stimulation on human monocyte derived macrophage (MDM) HO‐1 protein expression and elucidate the mechanisms by which IFNs cause dysregulation of HO‐1 protein. To address this, we treated primary human MDMs with type 1 or type 2 IFNs for 24 hours or 10 days. We collected protein lysates for western blot analysis and total RNA for quantitative PCR. Supernatants were collected to measure glutamate production and supernatant neurotoxicity. We observed that chronic type 1 and type 2 IFN stimulation (0.1 ng/ml) did not alter HO‐1 protein expression, however, we observed increased HO‐1 RNA expression with chronic type 1 IFN stimulation. Furthermore, we observed increased immunoproteosome subunit expression and loss of constitutive proteasome expression. No differences were observed in glutamate production or supernant neurotoxicity. These results suggest that chronic type 1 and type 2 IFN stimulation induce immunoproteasome expression and can subsequently lead to accelerated HO‐1 protein degradation, which may contribute to neurodegeneration. Support or Funding Information I would like to thank Mr. Rolando Garza and Dr. Dennis L. Kolson for their insightful comments and for allowing me to aid with their research project this summer. I would also like to express my gratitude towards my program advisors, Dr. Arnaldo Diaz Vazquez and Dr. Raquel Castellanos, the Office of Research and Diversity Training at Penn, and the following organizations that made this opportunity possible: MARC program @ UPR‐RP (NIH Grant 5T34GM007821‐37) and the Perelman School of Medicine @ UPenn. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .