Fumonisin B1-induced localized activation of cytokine network in mouse liver.
Fumonisin B1 (FB1), a mycotoxin produced primarily by Fusarium veticillioides and related fungi, is a carcinogen and causative agent of various animal diseases. Our previous studies indicated the involvement of tumor necrosis factor-alpha (TNFalpha) in FB1-induced hepatotoxicity. Male B6,129 mice (five/group) were injected subcutaneously with vehicle or 2.25 mg/kg/day of FB1 for 5 days and sampled 1 day after the last treatment. FB1 treatment caused an increased expression of TNFalpha, interferon gamma (IFNgamma) and interleukin (IL)-12 p40 in liver without any changes in kidney or spleen, suggesting the localized site of their production. IL-1beta cytokine expression was increased in liver and kidney after FB1 exposure. Cells involved in TNFalpha production after FB1 treatment in liver were identified as Kupffer cells. FB1 increased alanine aminotransferase in plasma and increased apoptotic cells in liver. Selective increase in proinflammatory T helper (Th)1-cytokines (IL-12 and IFNgamma) and TNFalpha with no alteration in Th2-cytokines (IL-4, IL-6 and IL-10) suggest the involvement of IL-12, produced by Kupffer cells, in induction of IFNgamma production by natural killer (NK) cells and/or NK1+ T cells, which can undergo a positive amplification loop with TNFalpha produced by macrophages or other hepatic cells to elicit the toxic reaction.
Bhandari
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Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens 30602, USA.
Brown
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CC
Sharma
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D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D056486:Chemical and Drug Induced Liver Injury; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D037341:Fumonisins / Q000008:administration & dosage / Q000633:toxicity*; D015870:Gene Expression; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics; D016753:Interleukin-10 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007668:Kidney / Q000737:chemistry; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009183:Mycotoxins / Q000633:toxicity*; D013154:Spleen / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D037341:Fumonisins; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D009183:Mycotoxins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; C056933:fumonisin B1; D007371:Interferon-gamma; D000410:Alanine Transaminase