Humans ; MicroRNAs ; therapeutic use ; Molecular Targeted Therapy

Humans ; Pneumonia ; Pulmonary Fibrosis ; T-Lymphocytes, Regulatory ; Th17 Cells

Humans ; Laminin ; Pulmonary Fibrosis

OBJECTIVETo explore whether the tagging single nucleotide polymorphisms (SNPs) within EPHX1 gene were involved in the genetic susceptibility to coal worker's pneumoconiosis (CWP) by case-control study.

METHODSThis study consisted of 697 CWP patients and 694 controls. All the subjects were Han Chinese, underground coal miners and recruited from coal mines of Xuzhou Mining Business Group Co Ltd.. The venous blood samples were obtained from all subjects and extracted genome DNA from the isolated leucocytes. Three SNPs were selected from the HapMap and the genotyping was done by the TaqMan method with the ABI 7900HT Real Time PCR system.

RESULTSThe Single SNP analyses showed that the genotype frequencies of EPHX1 (rs2234922) was significantly associated with decreased risk of CWP under co-dominant model (OR = 0.22, 95% CI = 0.06~0.79, P = 0.020), recessive model (OR = 0.23, 95% CI = 0.06~0.82, P = 0.023), and addictive model (OR = 0.75, 95% CI = 0.58~0.96, P = 0.022). The further stratification analysis showed that the risk of CWP will significantly decreased in non-smoking groups (OR = 0.10, 95% CI = 0.01~0.83, P = 0.033).

CONCLUSIONSOur results suggest that individuals with the EPHX1 (rs223492) GG genotype was associated with a dereased risk of CWP, and it has a protective effect on the developing CWP.

Anthracosis ; genetics ; Case-Control Studies ; Coal ; Epoxide Hydrolases ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Risk Factors ; Sequence Analysis, DNA

OBJECTIVETo investigate the regulatory effect of miR-149 on interleukin-6 (IL-6) expression in silica-induced pulmonary fibrosis.

METHODSA mouse model of pulmonary fibrosis was established using silica dust; the level of miR-149 in the lung tissues of mice with silica-induced pulmonary fibrosis was measured by quantitative real-time polymerase chain reaction (qRT-PCR), while the protein expression of IL-6 was measured by immunohistochemistry and Western blot. Type II alveolar epithelial cells (A549) and bronchial epithelial cells (HBE) were exposed to silica dust to establish a model; the level of miR-149 was measured by qRT-PCR, while the protein expression of IL-6 was measured by Western blot. A549 cells were transfected with miR-149 mimics and inhibitor in vitro, and the cellular expression of IL-6 was measured by Western blot. Serum samples from patients with coal workers' pneumoconiosis were examined by double-antibody sandwich ELISA to measure the protein expression of IL-6.

RESULTSAt three time points after silica treatment, the miR-149 expression in lung tissues was significantly down-regulated while an evident increase in IL-6 expression was observed in lung tissues (P < 0.01). Silica-stimulated epithelial cell (A549 and HBE) had up-regulated IL-6 expression and down-regulated miR-149 expression (P < 0.01). Increased levels of miR-149 attenuated IL-6 expression, whereas adverse results were found when miR-149 was inhibited. Compared with that in control group, serum level of IL-6 was significantly increased in patients with stage II and III coal workers' pneumoconiosis (P < 0.01).

CONCLUSIONDown-regulation of miR-149 and up-regulation of IL-6 might be involved in the progression of silica-induced pulmonary fibrosis; miR-149 could negatively regulate IL-6 expression.

Animals ; Anthracosis ; blood ; Cells, Cultured ; Disease Models, Animal ; Humans ; Interleukin-6 ; blood ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs ; metabolism ; Pulmonary Fibrosis ; chemically induced ; Silicon Dioxide ; toxicity