Possible effect of gene polymorphisms on the release of TNFα and IL1 cytokines in coal workers' pneumoconiosis.

It has been shown that coal dust exposure stimulates inflammatory response leading to increased release of cytokines from monocytes such as TNF-alpha and IL1. These released cytokines play the key role in the pathogenesis of pneumoconiosis including coal workers' pneumoconiosis. In this study, we investigated TNFA, IL1A, IL1B and IL1RA genes variations on basal, lipopolysaccharide and coal dust-induced cytokine release from blood monocytes of homozygous allele and minor variant allele carriers in Turkish coal workers and CWP patients. According to the genotyping results, TNFA -238 gene polymorphism was found as a risk factor in CWP development (OR=3.79) and to in vitro results; release of both TNF-alpha and IL1 cytokines from the monocytes in CWP patients was significantly increased compared to the healthy workers. Also, LPS and coal dust stimulated release of TNF-alpha, which was significantly higher in allele 2 carriers compared to subjects carrying allele 1 in both the groups. These data suggest that the coal dust-induced release of TNF-alpha from monocytes may be a useful biomarker of CWP.

[1]  Martine A. Collart,et al.  Requirement of tumour necrosis factor for development of silica-induced pulmonary fibrosis , 1990, Nature.

[2]  P. Borm,et al.  Mechanistically Identified Suitable Biomarkers of Exposure, Effect, and Susceptibility for Silicosis and Coal-Worker'S Pneumoconiosis: A Comprehensive Review , 2006, Journal of toxicology and environmental health. Part B, Critical reviews.

[3]  E. Coligan Current protocols in immunology , 1991 .

[4]  P. Borm,et al.  Spontaneous and stimulated release of tumor necrosis factor-alpha (TNF) from blood monocytes of miners with coal workers' pneumoconiosis. , 1988, The American review of respiratory disease.

[5]  I. D. Johnston,et al.  Increased risk of fibrosing alveolitis associated with interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphisms. , 2000, American journal of respiratory and critical care medicine.

[6]  B. Wallaert,et al.  Production of tumor necrosis factor-alpha and interleukin-6 by human alveolar macrophages exposed in vitro to coal mine dust. , 1991, American Journal of Respiratory Cell and Molecular Biology.

[7]  M. Munakata,et al.  Antithetical effect of tumor necrosis factor-alphagene polymorphism on coal workers' pneumoconiosis (CWP). , 2005, American journal of industrial medicine.

[8]  I. Tekin,et al.  Association of cytokine gene polymorphisms in CWP and its severity in Turkish coal workers. , 2008, American journal of industrial medicine.

[9]  J. Bertrand,et al.  Effect of TNF and LTA polymorphisms on biological markers of response to oxidative stimuli in coal miners: a model of gene-environment interaction , 2003, Journal of medical genetics.

[10]  K A Kim,et al.  Potential biomarker of coal workers' pneumoconiosis. , 1999, Toxicology letters.

[11]  J S Yudkin,et al.  The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. , 1998, The Journal of clinical investigation.

[12]  Anthony Seaton,et al.  Occupational Lung Diseases , 2008 .

[13]  J. Lafitte,et al.  Secretion and mRNA expression of TNF alpha and IL-6 in the lungs of pneumoconiosis patients. , 1995, American journal of respiratory and critical care medicine.

[14]  B. Wallaert,et al.  Cytokines and cytokine network in silicosis and coal workers' pneumoconiosis. , 1995, The European respiratory journal.

[15]  P. Borm,et al.  Plasma levels of soluble tumour necrosis factor receptors are increased in coal miners with pneumoconiosis. , 1995, The European respiratory journal.

[16]  W. Ollier Cytokine genes and disease susceptibility. , 2004, Cytokine.

[17]  J. Witte,et al.  Relation between tumour necrosis factor polymorphism TNFα-308 and risk of asthma , 2002, European Journal of Human Genetics.

[18]  P. Borm,et al.  Genotype and phenotype in susceptibility to coal workers' pneumoconiosis. the use of cytokines in perspective. , 2001, The European respiratory journal. Supplement.

[19]  Y. Lim,et al.  Tumor necrosis factor-α gene promoter polymorphism in coal workers’ pneumoconiosis , 2002 .

[20]  M. Petri,et al.  A promoter polymorphism of tumor necrosis factor alpha associated with systemic lupus erythematosus in African-Americans. , 1997, Arthritis and rheumatism.

[21]  P. Borm,et al.  Polymorphisms in the promoter of the tumor necrosis factor-alpha gene in coal miners. , 1998, American journal of industrial medicine.

[22]  M. Munakata,et al.  Increased susceptibility to silicosis and TNF-alpha production in C57BL/6J mice. , 1995, American journal of respiratory and critical care medicine.

[23]  S. D'alfonso,et al.  A polymorphic variation in a putative regulation box of the TNFA promoter region , 2004, Immunogenetics.

[24]  J. Lafitte,et al.  Abnormal secretion of interleukin-1 and tumor necrosis factor alpha by alveolar macrophages in coal worker's pneumoconiosis: comparison between simple pneumoconiosis and progressive massive fibrosis. , 1990, Experimental lung research.

[25]  C. Franceschi,et al.  Neuroinflammation and the genetics of Alzheimer’s disease: The search for a pro-inflammatory phenotype , 2001, Aging.

[26]  Song-Lih Huang,et al.  Tumor Necrosis Factor- α Gene Polymorphism in Chronic Bronchitis , 1997 .

[27]  E. Wouters,et al.  Airflow obstruction and monocyte TNF release in coal workers. , 1994, Experimental lung research.

[28]  Douglas Landsittel,et al.  Association of tumor necrosis factor-α and interleukin-1 gene polymorphisms with silicosis , 2001 .

[29]  R. Płoski,et al.  A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1α polymorphism , 1995 .