title: Alteration of gene expression profiles of peripheral mononuclear blood cells by tobacco smoke: implications for periodontal diseases.
abstract: Alterations of the host response by tobacco smoke adversely affect the periodontium. In this study, we examined the effects of in vitro acute smoke exposure on changes in m-RNA expression of primary peripheral mononuclear blood cells through microarray analysis. Mononuclear blood cells were isolated from four healthy non-smokers and plated in culture wells. Half of the cells were then exposed to 5 min of tobacco smoke. Fluorescent c-DNA probes were prepared from the linearly amplified m-RNAs for each sample and hybridized to cDNA microarrays representing approximately 30000 human genes. Significant increases or decreases in m-RNA gene expression between non-smoke-exposed and smoke-exposed samples were identified by permutation t-test, as implemented by the Significance Analysis of Microarrays software package. After smoke exposure, the expression of 90 genes with known function was significantly elevated and the expression of 19 genes with known function was significantly depressed. In addition, 18 upregulated and 26 downregulated transcripts were expressed sequence tags with little information available on function. Approximately 20 of the significantly elevated genes had previously been reported in the literature to be associated with periodontal pathogenesis (fold changes in parentheses). These included plasminogen activator (4.4), Heat Shock Protein (Hsp) 40 kD (2.2), thrombomodulin (4.2), cytochrome c (1.8), COX-2 (2.6), interleukin-1a (1.4), chemokine ligand 1 (3.8), cathepsin L (2.0), and calgranulin A (2.1). In addition, several significantly elevated genes not previously reported in the literature may also play a role in periodontal pathogenesis, and thus warrant further investigation. These include Diphtheria toxin receptor (heparin-binding epidermal growth factor-like growth factor) (7.8), Hsp 10 kDa (1.7), Hsp 105 kD (2.1), Hsp 70 kDa (1.6), and mitogen activated protein kinase 3 (1.5). Among the significantly depressed genes that may play a protective or destructive role in periodontal pathogenesis were interferon gamma receptor 2 (0.58) and chemokine receptor 2 (0.24). Our results may be of use in the search for the molecular mechanisms for the adverse effects of tobacco smoke on the host response.
authors.affiliation: Department of Stomatology University of California, San Francisco, UCSF Comprehensive Cancer Center, San Francisco, CA 94143, USA. mirper@itsa.ucsf.edu
authors.forename: M I
authors.initials: MI
authors.lastname: Ryder
authors.forename: W
authors.initials: W
authors.lastname: Hyun
authors.forename: P
authors.initials: P
authors.lastname: Loomer
authors.forename: C
authors.initials: C
authors.lastname: Haqq
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010510:Periodontal Diseases / Q000209:etiology*; D012333:RNA, Messenger / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012906:Smoke / Q000009:adverse effects*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D006360:Heat-Shock Proteins; D018836:Inflammation Mediators; D012333:RNA, Messenger; D012906:Smoke