High mobility group box-1 protects against Aflatoxin G1-induced pulmonary epithelial cell damage in the lung inflammatory environment.

High mobility group box-1 protects against Aflatoxin G1-induced pulmonary epithelial cell damage in the lung inflammatory environment. Toxicol Lett. 2020 May 21;: Authors: Kang L, Guo N, Liu X, Wang X, Guo W, Xie SM, Liu C, Lv P, Xing L, Zhang X, Shen H Abstract Aflatoxin G1 (AFG1) is a member of the carcinogenic aflatoxin family. Our previous studies indicated that oral administration of AFG1 caused tumor necrosis factor (TNF)-〈-dependent inflammation that enhanced oxidative DNA damage in alveolar epithelial cells, which may be related to AFG1-induced lung carcinogenesis. High mobility group box-1 (HMGB1) is a nuclear DNA-binding protein; the intracellular and extracellular roles of HMGB1 have been shown to contribute to DNA repair and sterile inflammation. The role of HMGB1 in DNA damage in an aflatoxin-induced lung inflammatory environment was investigated in this study. Upregulation of HMGB1, TLR2, and RAGE was observed in AFG1-induced lung inflamed tissues and adenocarcinoma. Blocking AFG1-induced inflammation by neutralization of TNF-〈 inhibited the upregulation of HMGB1 in mouse lung tissues, suggesting that AFG1-induced TNF-〈-dependent inflammation regulated HMGB1 expression. In the in vitro human pulmonary epithelial cell line model, Beas-2b, AFG1 directly enhanced the cytosolic translocation of HMGB1 and its extracellular secretion. The addition of extracellular soluble HMGB1 protected AFG1-induced DNA damage through ...
Source: Toxicology Letters - Category: Toxicology Authors: Tags: Toxicol Lett Source Type: research