title: Aflatoxin B1 Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway.
abstract: The aim of the present study is to investigate whether aflatoxin B1 (AFB1)-induced immunotoxicity is associated with oxidative stress and the expression of extracellular regulated protein kinases (ERK) 1/2. The primary splenocytes isolated from healthy pigs were activated and proliferated by anti-pig-CD3 monoclonal antibodies (mAb) in the present experiment, which is an antigen-specific stimulant. Results indicated that cell proliferation and interleukin-2 (IL-2) production were significantly suppressed by AFB1 from 4 to 8 μg/mL in a dose-dependent manner compared to the control group. Furthermore, AFB1 significantly increased malondialdehyde (MDA) levels, decreased reduced glutathione (GSH) and total superoxide dismutase levels, and up-regulated p-ERK1/2 expression in the activated splenocytes. N-Acetyl-l-cysteine blocked anti-CD3-induced T-cell suppression by AFB1 through increasing intracellular concentrations of GSH levels, decreasing MDA levels, and down-regulated p-ERK1/2 expression, respectively. Inhibition of the ERK1/2 expression by ERK-specific iRNA attenuated the decrease of T-cell proliferation and IL-2 production induced by AFB1. It was concluded that AFB1 inhibits anti-CD3-induced lymphocyte proliferation and IL-2 production by the oxidative stress mediated ERK1/2 MAPK signaling pathway.
authors.affiliation: Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Hao
authors.affiliation: Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Shengchi
authors.initials: S
authors.lastname: Pan
authors.affiliation: Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Junfa
authors.initials: J
authors.lastname: Hu
authors.affiliation: Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Qian
authors.affiliation: Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Gan
authors.affiliation: Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Kehe
authors.initials: K
authors.lastname: Huang
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D013552:Swine; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016604:Aflatoxin B1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: ERK1/2; RNA interference; aflatoxin B1; anti-pig-CD3 mAb; primary porcine splenocytes