Microarray analysis of the effect of diesel exhaust particles on in vitro cultured macrophages

Diesel exhaust particles (DEP) have been reported to induce or aggravate pulmonary diseases, including cancer and asthma. Alveolar macrophages are important cellular targets for DEP and have important immunological and inflammatory properties in the response to foreign Substances in the lung. In vitro cultures of human THP-1 cells were differentiated to macrophages and were exposed to 1600 ng/ml DEP during 6 and 24 h. Global changes in gene expression were evaluated using cDNA microarrays containing about 13,000 cDNAs. Each gene on the microarray was present in duplicate. A colorflip experiment was also performed, resulting in four ratio Measurements for each gene, that were used to evaluate significance of the gene expression findings. Gene expression changes were very modest (<3-fold induction/repression). Less than 1% of all genes were significantly regulated by DEP. Considering the 6 h exposure data, 50 clones were up- and 39 were downregulated. For the 24 h exposure data, there were 54 upregulated and 60 downregulated genes. Nine genes (CYP1B1, THBD, IIIb, ITGB7, SEC6, TNFRSFIB, LPXN, LOC51093 and BTG2) are upregulated and seven (PRDX1, CD36, PRKACB, BBOX1, CLK1, STMN1, and HMGB2) are downregulated at both time-points. Our data indicate the multitude of biological processes potentially influenced by DEP. (C) 2003 Elsevier Ltd. All rights reserved.