Impairment of alveolar type-II cells involved in the toxicity of Aflatoxin G1 in rat lung

Shen, Haitao; Lv, Ping; Xing, Xin; Xing, Lingxiao; Xia, Yan; Wang, Junling; Zhang, Xianghong

doi:10.1016/j.fct.2012.06.008

Cited by 11 publications

(7 citation statements)

References 52 publications

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“…Long‐term intragastric administration of AFG 1 induces lung adenocarcinoma in NIH mice, and the adenocarcinoma cells originate from lung alveolar type II (AT‐II) cells (Huang et al, ; Shen et al, ). We also found that AFG 1 induces ultrastructural and functional impairment in rat AT‐II cells in vitro and vivo (Shen et al, ). Activated AT‐II cells have been shown to be involved in lung carcinogenesis in several animal models (Li et al, ; Zanucco et al, ).…”

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confidence: 60%

“…Human alveolar type II epithelial A549 cells (ATCC) were routinely cultured in DMEM, supplemented with 100 U/ml penicillin, 100 U/ml streptomycin, and 10% fetal bovine serum (FBS) in 5% CO 2 /95% air. AFG 1 was diluted in DMSO (10 μg AFG 1 /μl DMSO) and added to the cultures to obtain final concentrations of 0.5, 2, and 4 mg/L according to our previous study (Shen et al, ). DMSO (0.1%) was added to A549 cells as a solvent control.…”

Section: Methodsmentioning

confidence: 99%

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Enhanced Phenotypic Alterations of Alveolar Type II Cells in Response to Aflatoxin G₁‐Induced Lung Inflammation

Shen

Liu

Shao

et al. 2015

Journal Cellular Physiology

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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.

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confidence: 60%

Section: Methodsmentioning

confidence: 99%

Enhanced Phenotypic Alterations of Alveolar Type II Cells in Response to Aflatoxin G₁‐Induced Lung Inflammation

Shen

Liu

Shao

et al. 2015

Journal Cellular Physiology

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“…At least 9 aquaporins are expressed in renal tissue, with aquaporin-1 found in the proximal complex tubes and descending thin tubes but not in other urinary tracts [23]. Among aflatoxins, the aflatoxin G1 is the most toxic one and is commonly found in animal and human foods, especially at high concentrations in cereals, such as corn, peanuts and non-alcoholic beer [24,25]. Aprevious study has suggested the role of aflatoxin G1 in disrupting spermatogenesis and reducing the sperm production and quality in mice [3].…”

Section: Introductionmentioning

confidence: 99%

Effects of Exposure to Aflatoxin G1 on the Plasma Biochemical Factors and Histopathological Properties of Renal Tissue in Mice

Zamir-Nasta

Ahmadi

Yazdkhasti

et al. 2021

IJT

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Background: Among aflatoxins, the subtype aflatoxin G1 is one of the most toxic, commonly found in cereals, legumes, dairy and non-alcoholic beers. Aflatoxins have been known as nephrotoxic compounds. In this study, changes in the expression of aquaporin-1, the histopathology of renal tissue and plasma biochemical factors after exposure to aflatoxin G1 were investigated in mice. Methods: Twenty-four adult male mice (weighing 20±2 g) were divided into four groups of six. The control group received the vehicle (0.2 ml) and the three experimental groups were injected intraperitoneally with aflatoxin G1 at 20 μg/kg for 7, 15 or 35 days, respectively. On days 7, 15 and 35, blood samples were drawn from the mice for biochemical analysis of plasma and the kidney tissues were sampled for real-time PCR and histopathological studies. Results: The real PCR results showed a reduction in aquaporin-1 expression in the experimental groups compared to those in the controls (P<0.05). Also, the plasma concentrations of urea and creatinine were significantly increased in the experimental groups compared to those in the controls (P<0.05). Also, the serum sodium and potassium levels had decreased significantly compared to the controls (P<0.05). Various damages were observed in the ureters and glomeruli among the experimental groups compared to those in the controls. Conclusion: Aflatoxin G1 had adverse effects on the renal tissue by reducing the expression of aquaporin-1. Subsequently, there were biochemical manifestations in the serum, consisting of changes in the concentrations of urea, creatinine, sodium and potassium, confirming the histopathological toxicity of aflatoxin G1.

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“…Then, we treated the mice with a soluble TNF-α receptor (sTNFR:Fc) and AFG 1 for 3 months and explored the role of TNF-α neutralization in AFG 1 -induced lung inflammatory responses, as well as DNA damage and CYP2A13 expression in AT-II cells. Our previous studies also showed that AFG 1 could induce structural impairment in rat AT-II cells, as well as cause oxidative DNA damage and apoptosis in the human AT-II cell line A549 (Shen, Lv et al, 2012;Shen et al, 2013). Finally, primary mice AT-II cells and A549 cells were applied and treated with AFG 1 and TNF-α to mimic the AFG 1 -induced TNF-α-related inflammatory responses in vitro.…”

Section: Introductionmentioning

confidence: 94%

Aflatoxin G₁ induced TNF‐α‐dependent lung inflammation to enhance DNA damage in alveolar epithelial cells

Shao

Guo

Wang

et al. 2018

Journal Cellular Physiology

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Aflatoxin G1 (AFG1), a member of the AF family with cytotoxic and carcinogenic properties, could cause DNA damage in alveolar type II (AT‐II) cells and induce lung adenocarcinoma. Recently, we found AFG1 could induce chronic lung inflammation associated with oxidative stress in the protumor stage. Chronic inflammation plays a critical role in cigarette smoke or benzo[a]pyrene‐induced lung tissues damage. However, it is unclear whether and how AFG1‐induced lung inflammation affects DNA damage in AT‐II cells. In this study, we found increased DNA damage and cytochrome P450 (CYP2A13) expression in AFG1‐induced inflamed lung tissues. Furthermore, we treated the mice with a soluble tumor necrosis factor (TNF)‐α receptor and AFG1 and found that TNF‐α neutralization inhibited the AFG1‐induced chronic lung inflammation in vivo, and then reversed the CYP2A13 expression and DNA damage in AT‐II cells. The results suggest that AFG1 induces TNF‐α‐dependent lung inflammation to regulate 2A13 expression and enhance DNA damage in AT‐II cells. Then, we treated the primary mice AT‐II cells and human AT‐II like cells (A549) with AFG1 and TNF‐α and found that TNF‐α enhanced the AFG1‐induced DNA damage in mice AT‐II cells as well as A549 cells in vitro. In AFG1‐exposed A549 cells, TNF‐α‐enhanced DNA damage and apoptosis were reversed by CYP2A13 small interfering RNA. Blocking NF‐κB pathway inhibited the TNF‐α‐enhanced CYP2A13 upregulation and DNA damage confirming that the CYP2A13 upregulation by TNF‐α plays an essential role in the activation of AFG1 under inflammatory conditions. Taken together, our findings suggest that AFG1 induces TNF‐α‐dependent lung inflammation, which upregulates CYP2A13 to promote the metabolic activation of AFG1 and enhance oxidative DNA damage in AT‐II cells.

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Impairment of alveolar type-II cells involved in the toxicity of Aflatoxin G1 in rat lung

Cited by 11 publications

References 52 publications

Enhanced Phenotypic Alterations of Alveolar Type II Cells in Response to Aflatoxin G₁‐Induced Lung Inflammation

Enhanced Phenotypic Alterations of Alveolar Type II Cells in Response to Aflatoxin G₁‐Induced Lung Inflammation

Effects of Exposure to Aflatoxin G1 on the Plasma Biochemical Factors and Histopathological Properties of Renal Tissue in Mice

Aflatoxin G₁ induced TNF‐α‐dependent lung inflammation to enhance DNA damage in alveolar epithelial cells

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Impairment of alveolar type-II cells involved in the toxicity of Aflatoxin G1 in rat lung

Cited by 11 publications

References 52 publications

Enhanced Phenotypic Alterations of Alveolar Type II Cells in Response to Aflatoxin G1‐Induced Lung Inflammation

Enhanced Phenotypic Alterations of Alveolar Type II Cells in Response to Aflatoxin G1‐Induced Lung Inflammation

Effects of Exposure to Aflatoxin G1 on the Plasma Biochemical Factors and Histopathological Properties of Renal Tissue in Mice

Aflatoxin G1 induced TNF‐α‐dependent lung inflammation to enhance DNA damage in alveolar epithelial cells

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Enhanced Phenotypic Alterations of Alveolar Type II Cells in Response to Aflatoxin G₁‐Induced Lung Inflammation

Enhanced Phenotypic Alterations of Alveolar Type II Cells in Response to Aflatoxin G₁‐Induced Lung Inflammation

Aflatoxin G₁ induced TNF‐α‐dependent lung inflammation to enhance DNA damage in alveolar epithelial cells