title: Enhanced phenotypic alterations of alveolar type II cells in response to Aflatoxin G1 -induced lung inflammation.
abstract: Recently, we discovered that Aflatoxin G1 (AFG1 ) induces chronic lung inflammatory responses, which may contribute to lung tumorigenesis in Balb/C mice. The cancer cells originate from alveolar type II cells (AT-II cells). The activated AT-II cells express high levels of MHC-II and COX-2, may exhibit altered phenotypes, and likely inhibit antitumor immunity by triggering regulatory T cells (Tregs). However, the mechanism underlying phenotypic alterations of AT-II cells caused by AFG1 -induced inflammation remains unknown. In this study, increased MHC-II expression in alveolar epithelium was observed and associated with enhanced Treg infiltration in mouse lung tissues with AFG1 -induced inflammation. This provides a link between phenotypically altered AT-II cells and Treg activity in the AFG1 -induced inflammatory microenvironment. AFG1 -activated AT-II cells underwent phenotypic maturation since AFG1 upregulated MHC-II expression on A549 cells and primary human AT-II cells in vitro. However, mature AT-II cells may exhibit insufficient antigen presentation, which is necessary to activate effector T cells, due to the absence of CD80 and CD86. Furthermore, we treated A549 cells with AFG1 and TNF-α together to mimic an AFG1 -induced inflammatory response in vitro, and we found that TNF-α and AFG1 coordinately enhanced MHC-II, CD54, COX-2, IL-10, and TGF-β expression levels in A549 cells compared to AFG1 alone. The phenotypic alterations of A549 cells in response to the combination of TNF-α and AFG1 were mainly regulated by TNF-α-mediated induction of the NF-κB pathway. Thus, enhanced phenotypic alterations of AT-II cells were induced in response to AFG1 -induced inflammation. Thus, AT-II cells are likely to suppress anti-tumor immunity by triggering Treg activity.
authors.affiliation: Lab of Pathology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Shen
authors.forename: Chunping
authors.initials: C
authors.lastname: Liu
authors.forename: Peilu
authors.initials: P
authors.lastname: Shao
authors.forename: Li
authors.initials: L
authors.lastname: Yi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Emily
authors.initials: E
authors.lastname: Mills Ko
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Tian
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Xing
authors.forename: Xianghong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000348:Aflatoxins / Q000494:pharmacology*; D056809:Alveolar Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000348:Aflatoxins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C027955:aflatoxin G1