In:
Journal of Cellular Physiology, Wiley, Vol. 230, No. 6 ( 2015-06), p. 1199-1211
Abstract:
Recently, we discovered that Aflatoxin G 1 (AFG 1 ) 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 AFG 1 ‐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 AFG 1 ‐induced inflammation. This provides a link between phenotypically altered AT‐II cells and Treg activity in the AFG 1 ‐induced inflammatory microenvironment. AFG 1 ‐activated AT‐II cells underwent phenotypic maturation since AFG 1 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 AFG 1 and TNF‐α together to mimic an AFG 1 ‐induced inflammatory response in vitro, and we found that TNF‐α and AFG 1 coordinately enhanced MHC‐II, CD54, COX‐2, IL‐10, and TGF‐β expression levels in A549 cells compared to AFG 1 alone. The phenotypic alterations of A549 cells in response to the combination of TNF‐α and AFG 1 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 AFG 1 ‐induced inflammation. Thus, AT‐II cells are likely to suppress anti‐tumor immunity by triggering Treg activity. J. Cell. Physiol. 230: 1199–1211, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Type of Medium:
Online Resource
ISSN:
0021-9541
,
1097-4652
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
1478143-8
SSG:
12
