{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:43:11Z","timestamp":1791189791735,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2000,8,1]],"date-time":"2000-08-01T00:00:00Z","timestamp":965088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Stimulation of human lung fibroblast cells with TGF-\u03b21 resulted in a transient burst of reactive oxygen species with maximal increase at 5 min after treatment. This reactive oxygen species increase was inhibited by the antioxidant, N-acetyl-l-cysteine (NAC). TGF-\u03b21 treatment stimulated IL-6 gene expression and protein synthesis in human lung fibroblast cells. Antioxidants including NAC, glutathione, and catalase reduced TGF-\u03b21-induced IL-6 gene expression, and direct H2O2 treatment induced IL-6 expression in a dose-dependent manner. NAC also reduced TGF-\u03b21-induced AP-1 binding activity, which is involved in IL-6 gene expression. It has been reported that Ca2+ influx is stimulated by TGF-\u03b21 treatment. EGTA suppressed TGF-\u03b21- or H2O2-induced IL-6 expression, and ionomycin increased IL-6 expression, with simultaneously modulating AP-1 activity in the same pattern. PD98059, an inhibitor of mitogen-activated protein kinase (MAPK) kinase\/extracellular signal-related kinase kinase 1, suppressed TGF-\u03b21- or H2O2-induced IL-6 and AP-1 activation. In addition, TGF-\u03b21 or H2O2 increased MAPK activity which was reduced by EGTA and NAC, suggesting that MAPK is involved in TGF-\u03b21-induced IL-6 expression. Taken together, these results indicate that TGF-\u03b21 induces a transient increase of intracellular H2O2 production, which regulates downstream events such as Ca2+ influx, MAPK, and AP-1 activation and IL-6 gene expression.<\/jats:p>","DOI":"10.4049\/jimmunol.165.4.2190","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:29:56Z","timestamp":1398025796000},"page":"2190-2197","source":"Crossref","is-referenced-by-count":126,"title":["Requirement of Hydrogen Peroxide Generation in TGF-\u03b21 Signal Transduction in Human Lung Fibroblast Cells: Involvement of Hydrogen Peroxide and Ca2+ in TGF-\u03b21-Induced IL-6 Expression"],"prefix":"10.1093","volume":"165","author":[{"given":"Eunsung","family":"Junn","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, Korea Research Institute of Bioscience and Biotechnology , Taejon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kee Nyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Korea Research Institute of Bioscience and Biotechnology , Taejon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyang Ran","family":"Ju","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Korea Research Institute of Bioscience and Biotechnology , Taejon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hyun","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Korea Research Institute of Bioscience and Biotechnology , Taejon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Young","family":"Im","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Korea Research Institute of Bioscience and Biotechnology , Taejon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Sik","family":"Kang","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Korea Research Institute of Bioscience and Biotechnology , Taejon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biology, Yonsei University , Seoul ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Soo","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Ewha Womans University , Seoul ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwon Soo","family":"Ha","sequence":"additional","affiliation":[{"name":"Biomolecule Research Team, Korea Basic Science Institute , Taejon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zee Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Biomolecule Research Team, Korea Basic Science Institute , Taejon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue Goo","family":"Rhee","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inpyo","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Korea Research Institute of Bioscience and Biotechnology , Taejon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,8,15]]},"reference":[{"key":"2026020213120274400_R1","first-page":"9","volume-title":"J. 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