{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:08:43Z","timestamp":1783487323655,"version":"3.55.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Gene expression in intraorbital fat was studied in smokers (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =8) and nonsmokers (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =8) with severe active GO, as well as in subcutaneous fat in thyroid-healthy smokers (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =5) and nonsmokers (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =5) using microarray and real-time polymerase chain reaction (PCR).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      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\/\n                      <jats:italic toggle=\"yes\">IL-1B<\/jats:italic>\n                      \/(2.3-fold) and interleukin-6\/\n                      <jats:italic toggle=\"yes\">IL-6<\/jats:italic>\n                      \/(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\/\n                      <jats:italic toggle=\"yes\">HLA-DRB1<\/jats:italic>\n                      \/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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      IEGs,\n                      <jats:italic toggle=\"yes\">IL-1B<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">IL-6<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2014.0153","type":"journal-article","created":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T07:19:06Z","timestamp":1408432746000},"page":"1524-1532","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":29,"title":["Smoking Induces Overexpression of Immediate Early Genes in Active Graves' Ophthalmopathy"],"prefix":"10.1177","volume":"24","author":[{"given":"Tereza","family":"Planck","sequence":"first","affiliation":[{"name":"Sk\u00e5ne University Hospital","place":["Sweden"]},{"name":"Lund University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bushra","family":"Shahida","sequence":"additional","affiliation":[{"name":"Lund University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemang","family":"Parikh","sequence":"additional","affiliation":[{"name":"YouGenomics LLC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristoffer","family":"Str\u00f6m","sequence":"additional","affiliation":[{"name":"Lund University","place":["Sweden"]},{"name":"Mid Sweden University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"\u00c5sman","sequence":"additional","affiliation":[{"name":"Lund University","place":["Sweden"]},{"name":"Sk\u00e5ne University Hospital","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5kan","family":"Brorson","sequence":"additional","affiliation":[{"name":"Lund University","place":["Sweden"]},{"name":"Sk\u00e5ne University Hospital","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt","family":"Hallengren","sequence":"additional","affiliation":[{"name":"Sk\u00e5ne University Hospital","place":["Sweden"]},{"name":"Lund University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Lantz","sequence":"additional","affiliation":[{"name":"Sk\u00e5ne University Hospital","place":["Sweden"]},{"name":"Lund University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,10,1]]},"reference":[{"key":"e_1_3_3_2_2","first-page":"998","article-title":"Thyrotropin receptor expression in Graves' orbital adipose\/connective tissues: potential autoantigen in Graves' ophthalmopathy","volume":"83","author":"Bahn RS","year":"1998","unstructured":"Bahn RS, , Dutton CM, , Natt N, , Joba W, , Spitzweg C, , Heufelder AE. 1998. 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