Aflatoxin G1 reduces the molecular expression of HLA-I, TAP-1 and LMP-2 of adult esophageal epithelial cells in vitro.
Aflatoxins (AF) are the mycotoxin with the carcinogenic effect produced by the fungi like Aspergillus flavus, including AFB(1), B(2), G(1), G(2), M(1), and so on. The detection rate of Aflatoxin G(1) (AFG(1)) is very high in the diet of residents in the high incidence area of the gastric carcinoma and esophageal carcinoma in China, which is the main polluting mycotoxin of the local grain. However, there were no available data regarding the gastric toxicity of AFG(1) up to now. In the present study, The toxicity of AFG(1)in vitro-cultured human primary adult esophageal epithelial cells was explored by employing the methods of Western blot, semi-quantitative RT-PCR and observing the effect of AFG(1) on the expression of the HLA-I molecules of the human esophageal epithelial cells and the antigen processing relative genes TAP-1 and LMP-2. The results showed that AFG(1) treatment could decrease both the protein expression of HLA-ABC of the cell surface and the mRNA expression of HLA-A and HLA-B. Moreover, In the AFG(1) treatment groups of different densities, both the TAP-1 mRNA and protein expression level of the human esophageal epithelial cells decreased. Furthermore, the LMP-2 protein expression level of the human esophageal epithelial cells decreased, while the mRNA expression level was not obviously changed by AFG(1) treatment. It is indicated that the decrease of the HLA-I expression of the cell surface was probably dependent on the decrease of the TAP-1 and LMP-2 expression to a great extent. The decrease of LMP-2 expression resulted in the decrease of HLA-I expression and stability in the cell membrane and finally led to the defect in the antigen presentation, which hindered its identification by the T lymphocytes, made it escape the immune surveillance, and then caused the tumor genesis.
Li
Zengning
Z
Department of nutrition, The First Attached Hospital, Hebei Medical University, Shijiazhuang, China. Zengningli@hebmu.edu.cn
Cui
Jinfeng
J
Zhang
Xianghong
X
Kang
Weijun
W
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000328:Adult; D000348:Aflatoxins / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004947:Esophagus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006680:HLA Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000348:Aflatoxins; D002273:Carcinogens; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C071313:LMP-2 protein; C027955:aflatoxin G1; D003546:Cysteine Endopeptidases