title: Smoking induces overexpression of immediate early genes in active Graves' ophthalmopathy.
abstract: BACKGROUND
  Cigarette smoking is a risk factor for the development of Graves' ophthalmopathy (GO). In a previous study of gene expression in intraorbital fat, adipocyte-related immediate early genes (IEGs) were overexpressed in patients with GO compared to controls. We investigated whether IEGs are upregulated by smoking, and examined other pathways that may be affected by smoking.
  
  
  METHODS
  Gene expression in intraorbital fat was studied in smokers (n=8) and nonsmokers (n=8) with severe active GO, as well as in subcutaneous fat in thyroid-healthy smokers (n=5) and nonsmokers (n=5) using microarray and real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  With microarray, eight IEGs were upregulated more than 1.5-fold in smokers compared to nonsmokers with GO. Five were chosen for confirmation and were also overexpressed with real-time PCR. Interleukin-1 beta/IL-1B/(2.3-fold) and interleukin-6/IL-6/(2.4-fold) were upregulated both with microarray and with real-time PCR in smokers with GO compared to nonsmokers. Major histocompatibility complex, class II, DR beta 1/HLA-DRB1/was upregulated with microarray (2.1-fold) and with borderline significance with real-time PCR. None of these genes were upregulated in smokers compared to nonsmokers in subcutaneous fat.
  
  
  CONCLUSIONS
  IEGs, IL-1B, and IL-6 were overexpressed in smokers with severe active GO compared to nonsmokers, suggesting that smoking activates pathways associated with adipogenesis and inflammation. This study underlines the importance of IEGs in the pathogenesis of GO, and provides evidence for possible novel therapeutic interventions in GO. The mechanisms activated by smoking may be shared with other conditions such as rheumatoid arthritis.
authors.affiliation: 1 Department of Endocrinology, Skåne University Hospital , Malmö, Sweden .
authors.forename: Tereza
authors.initials: T
authors.lastname: Planck
authors.forename: Bushra
authors.initials: B
authors.lastname: Shahida
authors.forename: Hemang
authors.initials: H
authors.lastname: Parikh
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Ström
authors.forename: Peter
authors.initials: P
authors.lastname: Åsman
authors.forename: Håkan
authors.initials: H
authors.lastname: Brorson
authors.forename: Bengt
authors.initials: B
authors.lastname: Hallengren
authors.forename: Mikael
authors.initials: M
authors.lastname: Lantz
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D017781:Genes, Immediate-Early; D005819:Genetic Markers; D049970:Graves Ophthalmopathy / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D005819:Genetic Markers; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6