The effect of aflatoxin B1 on cytokine mRNA and corresponding protein levels in peritoneal macrophages and splenic lymphocytes.
Male CD-1 mice were used to test the in vivo effects of aflatoxin B1 (AFB1) on the genetic expression of major cytokines produced by macrophages (interleukin (IL)- 1 alpha, IL-6 and tumour necrosis factor alpha (TNF)) and splenic lymphocytes (IL-2, interferon gamma (IFN gamma), and IL-3), activated in vitro with lipopolysaccharide (LPS) and concanavalin A (Con A), respectively. Animals were treated with 0, 0.03, 0.145 or 0.7 mg AFB1/kg body weight orally every other day for 2 weeks. No significant effects of the toxin on the weights of liver, kidney, spleen, or thymus, or in red blood cell counts were noted, but white blood cell counts were significantly elevated at the low (0.03 mg/kg) dose. Cytokine mRNA levels were measured by Northern blots or cDNA amplification and the secreted protein levels were measured by immunoassay. AFB1 had a marked effect on macrophage-produced cytokines. The mRNA levels increased significantly at the low (IL-1 alpha) or medium dose (IL-6 and TNF), their corresponding protein levels were generally suppressed. The levels of IL-1 alpha secreted protein were significantly suppressed at all dosages, and those of IL-6 and TNF at the high dose. The low dose of AFB1 slightly decreased both mRNA and protein levels of lymphocytic IL-2, IFN gamma, and IL-3, only IL-2 mRNA decreasing significantly (P < or = 0.05). It appears that AFB1 treatment preferentially affects macrophage functions, and in particular, it decouples the close correlation usually observed between transcriptional and translational controls of IL-1 alpha, IL-6 and TNF production by these cells.
Dugyala
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Department of Physiology and Pharmacology, College of Veterinery Medicine, University of Georgia, Athens 30602-7389, USA.
Sharma
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D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism*; D013154:Spleen / Q000166:cytology
D016207:Cytokines; D012333:RNA, Messenger; D016604:Aflatoxin B1