{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:13:23Z","timestamp":1779912803060,"version":"3.53.1"},"reference-count":67,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"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":[[2014,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Th1 cytokines exert pleiotropic effects in Hashimoto's thyroiditis. Previous studies reported a downregulation of thyroperoxidase and dual oxidase (DUOX) protein and mRNA expression in thyroid cells treated with Th1 cytokines. Although this effect is partially mediated by intracellular reactive oxygen species (ROS) and reactive nitrogen species, the nature and the source of the ROS involved are currently unknown. The aim of this study was to examine further the nature and source of the ROS produced in response to Th1 cytokines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Two rat thyroid cell lines (PCCL3 and FRTL-5) and human thyrocytes were incubated with Th1 cytokines (interleukin [IL]-1\u03b1 and interferon-\u03b3) in the presence or absence of the Th2 cytokine IL-4, the nitric oxide synthase inhibitor N-nitroso-L-arginine methyl ester (L-NAME), or the synthetic antioxidant N-acetylcysteine. The nature and source of the intracellular and extracellular ROS produced were determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A rapid increase in intracellular ROS was observed in cells incubated with Th1 cytokines. This increase was not caused by extracellular hydrogen peroxide (H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      ) produced by DUOX because both DUOX expression and extracellular H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      synthesis were decreased by Th1 cytokines. Confocal colocalization experiments showed that the Th1 cytokine\u2013triggered ROS were not produced from mitochondria. Electron paramagnetic resonance investigations of PCCL3 cells indicated that the highly reactive hydroxyl radical was not involved in the response to Th1 cytokines.\n                      <jats:italic toggle=\"yes\">NOX2<\/jats:italic>\n                      mRNA expression was significantly increased in PCCL3 cells incubated with Th1 cytokines, as was the expression of the protein in the thyroid of Hashimoto's thyroiditis patients. NOX4 expression was by contrast unaffected. These results suggest that at least superoxide could be produced after exposure of thyroid cells to Th1 cytokines. The effects of L-NAME and IL-4, both of which partially or totally reverse Th1 cytokine\u2013induced effects, on ROS release were also analyzed. L-NAME and IL-4 significantly reduced the Th1 cytokine\u2013induced surge of intracellular ROS in PCCL3 and human thyroid cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      The data presented here reinforce the idea that ROS, other than extracellular H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      produced by DUOX, are released from NOX2 after exposure of thyroid cells to Th1 cytokines. ROS\/reactive nitrogen species act as important, but as further explained, not exclusive intracellular mediators of Th1 cytokine\u2013induced effects in thyroid cells.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2013.0142","type":"journal-article","created":{"date-parts":[[2013,9,27]],"date-time":"2013-09-27T16:44:42Z","timestamp":1380300282000},"page":"441-452","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Differential Regulation of the Production of Reactive Oxygen Species in Th1 Cytokine\u2013Treated Thyroid Cells"],"prefix":"10.1177","volume":"24","author":[{"given":"Ides M.","family":"Colin","sequence":"first","affiliation":[{"name":"Catholic University of Louvain","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Poncin","sequence":"additional","affiliation":[{"name":"Catholic University of Louvain","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Lev\u00eaque","sequence":"additional","affiliation":[{"name":"Catholic University of Louvain","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Gallez","sequence":"additional","affiliation":[{"name":"Catholic University of Louvain","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Catherine","family":"G\u00e9rard","sequence":"additional","affiliation":[{"name":"Catholic University of Louvain","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,3,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1996.d01-784.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-5428(97)00027-7"},{"key":"e_1_3_3_4_2","first-page":"324","article-title":"Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-1 alpha and interleukin-6","volume":"77","author":"Grubeck-Loebenstein B","year":"1989","unstructured":"Grubeck-Loebenstein B, , Buchan G, , Chantry D, , Kassal H, , Londei M, , Pirich K, , Barrett K, , Turner M, , Waldhausl W, , Feldmann M. 1989. 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