title: Differential immune modulation by deoxynivalenol (vomitoxin) in mice.
abstract: Mycotoxin deoxynivalenol (DON), a secondary metabolite produced by Fusarium fungi, is a contaminant in wheat, barley, and corn worldwide. It has been suggested that DON exhibits toxicity in various organs. Due to the lack of immunotoxicity data for DON, we investigated the differential immunomodulatory effects of DON in mice. DON was orally administered to female BALB/c mice at a dose of 0, 0.5, or 2mg/kg body weight for 14 days and various immunotoxicity tests were performed with standard protocols. The population of CD19(+) and CD11c(+) cells in the spleen and mesenteric lymph node (MLN) and of F4/80(+) cells in the spleen was significantly decreased in DON-treated mice, whereas the level of CD8(+) and CD4(+)CD25(+)Foxp3(+) cells in the spleen and CD4(+) T cells in MLN was significantly increased. In intra-epithelial lymphocytes (IELs) of the small intestine, the population of CD4 (+) and CD19(+) cells was increased but that of CD8(+) cells was decreased. Levels of CD4 (+) and CD8(+) cells were decreased in lamina propria lymphocytes (LPLs) of small intestine; however, the level of CD4(+) and CD8(+) lymphocytes was increased but that of CD19(+) cells was decreased in Peyer's patches lymphocytes (PPLs). Normalized expression of TLR4 in spleen, TLR9 in PPs, and TLR2, TLR3 and TLR4 in MLNs was significantly decreased, whereas expression of TLR5 and TLR9 was increased in spleen. The concentration of IgA and IgE was decreased and increased, respectively, in serum; however, the mucosal IgA level was significantly increased in the duodenum. Levels of IFN-γ, IL-2, IL-4, and IL-6 were significantly increased in serum. Furthermore, DON induced apoptosis in spleen, MLNs, and PPs, and DON-induced apoptosis was promoted by increased expression of Bax and decreased expression of Bcl-2. The autophagy genes Atg5 and Beclin-1 were up-regulated in spleen but down-regulated in MLN. After priming of the RAW 264.7 macrophage cell line with different TLR ligands, DON exposure differentially modulated IL-1β, IL-10, and TNF-α production. These results indicate that DON can cause various immunomodulatory effects in mice, creating a milieu that might allow invasion by other microorganisms.
authors.affiliation: Biosafety Research Institute and Laboratory of Pathology, College of Veterinary Medicine, Chonbuk National University, Jeonju 561-756, South Korea.
authors.forename: Mohammad Rafiqul
authors.initials: MR
authors.lastname: Islam
authors.affiliation: Biosafety Research Institute and Laboratory of Pathology, College of Veterinary Medicine, Chonbuk National University, Jeonju 561-756, South Korea.
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Roh
authors.affiliation: Advanced Analysis Team, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Korea Food & Drug Administration, 363-951, South Korea.
authors.forename: Jinho
authors.initials: J
authors.lastname: Kim
authors.affiliation: Biosafety Research Institute and Laboratory of Pathology, College of Veterinary Medicine, Chonbuk National University, Jeonju 561-756, South Korea.
authors.forename: Chae Woong
authors.initials: CW
authors.lastname: Lim
authors.affiliation: Biosafety Research Institute and Laboratory of Pathology, College of Veterinary Medicine, Chonbuk National University, Jeonju 561-756, South Korea. Electronic address: bskims@jbnu.ac.kr.
authors.forename: Bumseok
authors.initials: B
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation; D005260:Female; D007070:Immunoglobulin A / Q000097:blood; D056747:Immunomodulation / Q000502:physiology*; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010581:Peyer's Patches / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D014255:Trichothecenes / Q000494:pharmacology*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; C494827:Bax protein, mouse; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D016207:Cytokines; D007070:Immunoglobulin A; D008869:Microtubule-Associated Proteins; D051193:Toll-Like Receptors; D014255:Trichothecenes; D051028:bcl-2-Associated X Protein; C007262:deoxynivalenol
keywords: Apoptosis; Autophagy; Cytokines; Deoxynivalenol; IgA; Immune cells