Dataset Information

Effects of chemical composition on the lung cell response to coal particles: Implications for coal workers' pneumoconiosis.

ABSTRACT:

Background and objective

Coal mine dust has a complex and heterogeneous chemical composition. It has been suggested that coal particle chemistry plays a critical role in determining the pathogenesis of coal workers' pneumoconiosis (CWP). In this study, we aimed to establish the association between the detrimental cellular response and the chemical composition of coal particles.

Methods

We sourced 19 real-world coal samples. Samples were crushed prior to use to minimize the impact of particle size on the response and to ensure the particles were respirable. Key chemical components and inorganic compounds were quantified in the coal samples. The cytotoxic, inflammatory and pro-fibrotic responses in epithelial cells, macrophages and fibroblasts were assessed following 24 h of exposure to coal particles. Principal component analysis (PCA) and stepwise regression were used to determine which chemical components of the coal particles were associated with the cell response.

Results

The cytotoxic, inflammatory and pro-fibrotic response varied considerably between coal samples. There was a high level of collinearity in the cell responses and between the chemical compounds within the coal samples. PCA identified three factors that explained 75% of the variance in the cell response. Stepwise multiple regression analysis identified K₂ O (p <0.001) and Fe₂ O₃ (p = 0.011) as significant predictors of cytotoxicity and cytokine production, respectively.

Conclusion

Our data clearly demonstrate that the detrimental cellular effects of exposure to coal mine dusts are highly dependent on particle chemistry. This has implications for understanding the pathogenesis of CWP.

SUBMITTER: Song Y

PROVIDER: S-EPMC9314662 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The interleukin 17A (IL-17A) which is located on chromosome 6p and has been linked to chronic inflammation, is an important candidate gene conferring coal workers' pneumoconiosis (CWP). The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of IL-17A and CWP in a Chinese population.We conducted a case-control study to investigate the role of four common SNPs in the IL-17A gene, and evaluated the relationship between these four SNPs and dust-exposure year, tobacco smoking and stages of CWP. A total of 1391 subjects was enrolled in this study, including 694 subjects in control group and 697 in case group. TaqMan based qRT-PCRs were taken to genotype rs2275913, rs3748067, rs4711998, and rs8193036 within the IL-17A gene. Luciferase assays were used to determine the effects of rs8193036 C?>?T alleles on the expression of IL-17A.Unconditional logistic regression analysis showed that the genotypes of rs3748067 AA (adjusted OR?=?0.43, 95 % CI?=?0.23-0.83) and rs8193036 TT (adjusted OR?=?0.59, 95 % CI?=?0.40-0.86) were associated with a decreased risk of CWP, particularly among subgroups of smokers (adjusted OR =0.34, 95 % CI?=?0.13-0.86 for rs3748076; adjusted OR?=?0.41, 95 % CI?=?0.23-0.71 for 8193036) and CWP cases with stage I (adjusted OR?=?0.45, 95 % CI?=?0.21-0.98 for rs3748076; adjusted OR?=?0.46, 95 % CI?=?0.28-0.74 for 8193036). Furthermore, the polymorphism of rs3748067 significantly reduced the CWP risk among cases with over 27 years of dust exposure (adjusted OR?=?0.42, 95 % CI?=?0.18-0.97). The luciferase assays in two cell lines showed that the rs8193036 C?>?T substitution could reduce the expression of IL-17A, which was consistent with the findings of our association study.The rs3748067 G?>?A and rs8193036 C?>?T polymorphisms decrease CWP risk. These findings could be helpful in identifying individuals at decreased risk for CWP and further studies are warranted to validate them.