Cytochrome P450 isoforms are differently up-regulated in aflatoxin B1-exposed human lymphocytes and monocytes. (February 2014)

• Record Type: Journal Article
• Authors: Bahari, Abbas; Mehrzad, Jalil; Mahmoudi, Mahmoud; Bassami, Mohammad Reza; Dehghani, Hesam
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 36:Number 1(2014:Feb.)
• Page Start: 1
• Page End: 10
• Publication Date: 2014-02
• Subjects: Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.3109/08923973.2013.850506
• Languages: English
• ISSNs: 0892-3973

Abstract

<abstract> <title>Abstract</title> <p> <italic>Context</italic>: Aflatoxins (AFs) are highly hazardous mycotoxins with potent carcinogenic, mutagenic and immune disregulatory properties. Cytochrome P450 (<italic>CYP</italic>) isoforms are central for enhanced AFB<sub>1</sub> toxicity <italic>in situ</italic>. It remains to be seen whether and how these AFB<sub>1</sub> activators work in human leukocytes.</p> <p> <italic>Objective</italic>: To investigate the involvement of <italic>CYP</italic> isoforms in AFB<sub>1</sub> toxicity of circulating mononuclear cells, we examined the impact of environmentally relevant levels of AFB<sub>1</sub> on lymphocytes and monocytes.</p> <p> <italic>Materials and methods</italic>: Very low and moderate doses of AFB<sub>1</sub> with/without <italic>CYP</italic> inducers on transcription of key <italic>CYP</italic> isoforms and toll-like receptor 4 (<italic>TLR4</italic>) were examined in human lymphocytes, monocytes and HepG2 cells; cell cycle distribution and viability were also analyzed in AFB<sub>1</sub>-exposed lymphocytes and monocytes.</p> <p> <italic>Results</italic>: Only <italic>CYP1A1, CYP1B1, CYP3A4, CYP3A5</italic> and <italic>CYP3A7</italic> expressed in lymphocytes and monocytes. <italic>TLR4</italic> much more expressed in monocytes than in lymphocytes, but HepG2 showed little <italic>TLR4</italic> transcription. While <italic>CYP1A1, CYP1B1</italic> and <italic>CYP3A4</italic> were highly induced by AFB<sub>1</sub> in monocytes, in lymphocytes only <italic>CYP1A1</italic> was induced. Among <italic>CYP1A1, CYP1B1</italic> and <italic>CYP3A4</italic> only <italic>CYP1A1</italic> responded to low and moderate levels of AFB<sub>1</sub>. Enhanced transcripts of <italic>CYPs</italic> by AFB<sub>1</sub> yielded little synergies on <italic>TLR4</italic> transcription in lymphocytes and monocytes. Cell cycle arrest and necrosis were also detected in AFB<sub>1</sub>-exposed lymphocytes and monocytes.</p> <p> <italic>Conclusions</italic>: Our novel findings indicate that AFB<sub>1</sub> more intensively stimulates <italic>CYP</italic> genes expression in monocytes than in lymphocytes. Mechanistically, this could explain a more pronounced immunotoxicity of AFB<sub>1</sub> in myeloid than in lymphoid lineage cells <italic>in vitro/situ/vivo</italic>.</p> </abstract>