title: Biologically relevant doses of mixed aflatoxins B and G up-regulate MyD88, TLR2, TLR4 and CD14 transcripts in human PBMCs.
abstract: BACKGROUND
  Aflatoxins (AFs) are highly hazardous carcinogenic mycotoxins originated from very common fungi present in the environment. Their effect on key immune-surveillance molecules is unclear.
  
  
  OBJECTIVE
  We aimed to examine the effect of mixed AFs on immunologically relevant molecules and on viability in human peripheral blood mononuclear cells (PBMCs), in conditions similar to those occurring naturally, i.e. using a mixture of environmentally relevant levels of AFB₁, AFB₂, AFG₁ and AFG₂.
  
  
  METHODS
  We evaluated the mRNA expression of MyD88, toll-like receptor (TLR)-2, TLR4 and CD14, in human PBMCs treated with a mixture of AFB₁, AFB₂, AFG₁ and AFG₂ at different doses for 2, 12 and 24 h. We used qRT-PCR to assess changes in transcripts of MyD88, TLR2, TLR4 and CD14 in PBMCs. We also evaluated the viability of PBMCs exposed to AFs.
  
  
  RESULTS
  Biologically relevant levels of mixed AFs elicited early immune modulation in human PBMCs. qRT-PCR results showed several folds increase of MyD88, TLR2, TLR4 and CD14 transcripts in PBMCs as early as 2 h post-exposure to mixed AFs. Kinetics and dose-response of the up-regulation differed for mentioned gene transcripts. Further, prolonged exposure to mixed AFs decreased PBMCs viability.
  
  
  CONCLUSIONS
  Immunotoxicity of AFs on PBMCs may be mediated by up-regulation of key immune-surveillance molecule transcripts. The description of these effects induced by AFs on PBMCs are novel and should be taken into account when considering AF-related infectious and noninfectious diseases in areas highly exposed to AFs.
authors.affiliation: Department of Biochemistry, Faculty of Science, Payam Noor University of Mashhad, Iran. mehrzad@um.ac.ir
authors.forename: Amir Mohammad
authors.initials: AM
authors.lastname: Malvandi
authors.forename: Jalil
authors.initials: J
authors.lastname: Mehrzad
authors.forename: Masoud
authors.initials: M
authors.lastname: Saleh-moghaddam
mesh_terms: D000328:Adult; D016604:Aflatoxin B1 / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000276:immunology*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis / Q000276:immunology*; D011042:Poisons / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects* / Q000276:immunology
chemical_list: D018950:Lipopolysaccharide Receptors; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D011042:Poisons; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016604:Aflatoxin B1