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Gene expression profile and toxic effects in human bronchial epithelial cells exposed to zearalenone.

So MY, Tian Z, Phoon YS, Sha S, Antoniou MN, Zhang J, Wu RS, Tan-Un KC - PLoS ONE (2014)

Bottom Line: The array results showed that after ZEA treatment, 262 genes at 6 h and 1073 genes at 24 h were involved in the differential regulation.Results of further experiments indicated that 40 µM ZEA decreased cell viability, induced apoptosis and promoted reactive oxygen species (ROS) generation in a time-dependent manner.Immuno-suppressive effects of ZEA were further revealed through the suppression of lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines (IL-6, IL-8 and IL-1β).

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong SAR, China.

ABSTRACT
Zearalenone (ZEA), a mycoestrogen produced by Fusarium fungal species, is mainly found in cereal crops such as maize, wheat and barley. Although ZEA has been reported to be present in air, little is known about the health risk or the molecular basis of action when lung cells are exposed to ZEA. As ZEA has a similar structure to estrogen, its potential risk as an endocrine disrupting chemical (EDC) has thus aroused both environmental and public health concerns. The purpose of this study is to identify the responses and underlying molecular changes that occur when human bronchial epithelial BEAS-2B cells are exposed to ZEA. Differential gene expression profiles were identified in cells that were treated with 40 µM ZEA for 6 h and 24 h by high-throughput microarray analysis using Affymetrix Human Gene 2.0 GeneChip. The array results showed that after ZEA treatment, 262 genes at 6 h and 1073 genes at 24 h were involved in the differential regulation. Pathway analysis revealed that diverse cellular processes were affected when lung cells were exposed to ZEA resulting in impaired response to DNA damage, cell cycle arrest, down-regulation of inflammatory responses and alterations of epigenetic marks. Results of further experiments indicated that 40 µM ZEA decreased cell viability, induced apoptosis and promoted reactive oxygen species (ROS) generation in a time-dependent manner. Immuno-suppressive effects of ZEA were further revealed through the suppression of lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines (IL-6, IL-8 and IL-1β). Interestingly, the level of global DNA methylation was markedly decreased after 24 h exposure to ZEA. Collectively, these observations suggested that a broad range of toxic effects are elicited by ZEA. Particularly, ROS may play a pivotal role in ZEA-induced cell death. These adverse effects observed in lung cells suggest that exposure to ZEA may increase susceptibility of lung cells to diseases and required further investigations.

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Related in: MedlinePlus

Quantitative PCR showing mRNA expression of inflammatory cytokines and chemokines in LPS stimulated BEAS-2B cells.The mRNA expression of β–actin was used for normalization. (A) Interleukin 6 (IL-6). (B) Interleukin 8 (IL-8). (C) Interleukin 1, beta (IL-1β). Results represent the mean± SD of at least 3 independent experiments and bars with different alphabets show significant differences (One-way ANOVA, p<0.05).
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pone-0096404-g006: Quantitative PCR showing mRNA expression of inflammatory cytokines and chemokines in LPS stimulated BEAS-2B cells.The mRNA expression of β–actin was used for normalization. (A) Interleukin 6 (IL-6). (B) Interleukin 8 (IL-8). (C) Interleukin 1, beta (IL-1β). Results represent the mean± SD of at least 3 independent experiments and bars with different alphabets show significant differences (One-way ANOVA, p<0.05).

Mentions: Disturbingly, many of the pro-inflammatory responsive genes were down-regulated while those anti-inflammatory genes were up-regulated (Table 7). The anti-inflammatory effects of ZEA were further revealed in its ability to reduce lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines. After 6 h treatment, LPS alone induced the expressions of IL-6, IL-8 and IL-1β by 1.49, 1.37 and 1.29 folds, respectively. However, the inductions of these cytokines were significantly suppressed by ZEA (Figure 6).


Gene expression profile and toxic effects in human bronchial epithelial cells exposed to zearalenone.

So MY, Tian Z, Phoon YS, Sha S, Antoniou MN, Zhang J, Wu RS, Tan-Un KC - PLoS ONE (2014)

Quantitative PCR showing mRNA expression of inflammatory cytokines and chemokines in LPS stimulated BEAS-2B cells.The mRNA expression of β–actin was used for normalization. (A) Interleukin 6 (IL-6). (B) Interleukin 8 (IL-8). (C) Interleukin 1, beta (IL-1β). Results represent the mean± SD of at least 3 independent experiments and bars with different alphabets show significant differences (One-way ANOVA, p<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4008614&req=5

pone-0096404-g006: Quantitative PCR showing mRNA expression of inflammatory cytokines and chemokines in LPS stimulated BEAS-2B cells.The mRNA expression of β–actin was used for normalization. (A) Interleukin 6 (IL-6). (B) Interleukin 8 (IL-8). (C) Interleukin 1, beta (IL-1β). Results represent the mean± SD of at least 3 independent experiments and bars with different alphabets show significant differences (One-way ANOVA, p<0.05).
Mentions: Disturbingly, many of the pro-inflammatory responsive genes were down-regulated while those anti-inflammatory genes were up-regulated (Table 7). The anti-inflammatory effects of ZEA were further revealed in its ability to reduce lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines. After 6 h treatment, LPS alone induced the expressions of IL-6, IL-8 and IL-1β by 1.49, 1.37 and 1.29 folds, respectively. However, the inductions of these cytokines were significantly suppressed by ZEA (Figure 6).

Bottom Line: The array results showed that after ZEA treatment, 262 genes at 6 h and 1073 genes at 24 h were involved in the differential regulation.Results of further experiments indicated that 40 µM ZEA decreased cell viability, induced apoptosis and promoted reactive oxygen species (ROS) generation in a time-dependent manner.Immuno-suppressive effects of ZEA were further revealed through the suppression of lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines (IL-6, IL-8 and IL-1β).

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong SAR, China.

ABSTRACT
Zearalenone (ZEA), a mycoestrogen produced by Fusarium fungal species, is mainly found in cereal crops such as maize, wheat and barley. Although ZEA has been reported to be present in air, little is known about the health risk or the molecular basis of action when lung cells are exposed to ZEA. As ZEA has a similar structure to estrogen, its potential risk as an endocrine disrupting chemical (EDC) has thus aroused both environmental and public health concerns. The purpose of this study is to identify the responses and underlying molecular changes that occur when human bronchial epithelial BEAS-2B cells are exposed to ZEA. Differential gene expression profiles were identified in cells that were treated with 40 µM ZEA for 6 h and 24 h by high-throughput microarray analysis using Affymetrix Human Gene 2.0 GeneChip. The array results showed that after ZEA treatment, 262 genes at 6 h and 1073 genes at 24 h were involved in the differential regulation. Pathway analysis revealed that diverse cellular processes were affected when lung cells were exposed to ZEA resulting in impaired response to DNA damage, cell cycle arrest, down-regulation of inflammatory responses and alterations of epigenetic marks. Results of further experiments indicated that 40 µM ZEA decreased cell viability, induced apoptosis and promoted reactive oxygen species (ROS) generation in a time-dependent manner. Immuno-suppressive effects of ZEA were further revealed through the suppression of lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines (IL-6, IL-8 and IL-1β). Interestingly, the level of global DNA methylation was markedly decreased after 24 h exposure to ZEA. Collectively, these observations suggested that a broad range of toxic effects are elicited by ZEA. Particularly, ROS may play a pivotal role in ZEA-induced cell death. These adverse effects observed in lung cells suggest that exposure to ZEA may increase susceptibility of lung cells to diseases and required further investigations.

Show MeSH
Related in: MedlinePlus