title: Inflammatory transcriptome profiling of human monocytes exposed acutely to cigarette smoke.
abstract: BACKGROUND
  Cigarette smoking is responsible for 5 million deaths worldwide each year, and is a major risk factor for cardiovascular and lung diseases. Cigarette smoke contains a complex mixture of over 4000 chemicals containing 10(15) free radicals. Studies show smoke is perceived by cells as an inflammatory and xenobiotic stimulus, which activates an immune response. The specific cellular mechanisms driving cigarette smoke-induced inflammation and disease are not fully understood, although the innate immune system is involved in the pathology of smoking related diseases.
  
  
  RESULTS
  To address the impact of smoke as an inflammagen on the innate immune system, THP-1 cells and Human PBMCs were stimulated with 3 and 10% (v/v) cigarette smoke extract (CSE) for 8 and 24 hours. Total RNA was extracted and the transcriptome analysed using Illumina BeadChip arrays. In THP-1 cells, 10% CSE resulted in 80 genes being upregulated and 37 downregulated by ≥1.5 fold after 8 hours. In PBMCs stimulated with 10% CSE for 8 hours, 199 genes were upregulated and 206 genes downregulated by ≥1.5 fold. After 24 hours, the number of genes activated and repressed by ≥1.5 fold had risen to 311 and 306 respectively. The major pathways that were altered are associated with cell survival, such as inducible antioxidants, protein chaperone and folding proteins, and the ubiquitin/proteosome pathway.
  
  
  CONCLUSIONS
  Our results suggest that cigarette smoke causes inflammation and has detrimental effects on the metabolism and function of innate immune cells. In addition, THP-1 cells provide a genetically stable alternative to primary cells for the study of the effects of cigarette smoke on human monocytes.
authors.affiliation: Department of Cardiothoracic Pharmacology, Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: William R
authors.initials: WR
authors.lastname: Wright
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Parzych
authors.forename: Damian
authors.initials: D
authors.lastname: Crawford
authors.forename: Charles
authors.initials: C
authors.lastname: Mein
authors.forename: Jane A
authors.initials: JA
authors.lastname: Mitchell
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Paul-Clark
mesh_terms: D002460:Cell Line; D019992:Databases as Topic; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology*; D025341:Principal Component Analysis; D015398:Signal Transduction / Q000235:genetics; D012907:Smoking / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1