{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:13:56Z","timestamp":1777439636157,"version":"3.51.4"},"reference-count":9,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2013,2,7]],"date-time":"2013-02-07T00:00:00Z","timestamp":1360195200000},"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":[[2013,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The IL-6 amplifier, a positive feedback loop for NF\u03baB signaling, which was originally found to be activated by IL-17A and IL-6 stimulation in non-immune cells, is molecularly a simultaneous activator of NF\u03baB and signal transducer and activator of transcription 3 (STAT3), functionally a local chemokine inducer and pathologically a machinery for inflammation development. It has been shown that IL-6 amplifier activation in epithelial cells contributes to rejection responses in a mouse chronic rejection model that develops a bronchiolitis obliterans (BO)-like disease. We investigated whether the IL-6 amplifier is activated in BO regions of a human lung graft after allogeneic transplantation. NF\u03baB and STAT3 molecules were phosphorylated in the epithelial regions of bronchi that localized in the BO regions. Additionally, chemokine ligand 2 (CCL2), and CD4+ T cells and macrophages increased in these regions. Furthermore, human lung epithelial cells expressed CCL2 after stimulation by IFN\u03b3 in the presence of IL-6 and epidermal growth factor via enhanced STAT3 signaling, which parallels behavior seen in the mouse model. Thus, our results suggest that the IL-6 amplifier in the epithelial cells of grafts is involved in chronic rejection after lung transplantation, suggesting that the amplifier may be a valuable therapeutic target to prevent chronic rejection after lung transplantation.<\/jats:p>","DOI":"10.1093\/intimm\/dxs158","type":"journal-article","created":{"date-parts":[[2013,2,9]],"date-time":"2013-02-09T03:52:13Z","timestamp":1360381933000},"page":"319-332","source":"Crossref","is-referenced-by-count":39,"title":["IL-6 amplifier activation in epithelial regions of bronchi after allogeneic lung transplantation"],"prefix":"10.1093","volume":"25","author":[{"given":"Jihye","family":"Lee","sequence":"first","affiliation":[{"name":"Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine 1 , Osaka University, Osaka, 565\u20130871, Japan"},{"name":"WPI Immunology Frontier Research Center, Osaka University 2 , Osaka , 565\u20130871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Nakagiri","sequence":"additional","affiliation":[{"name":"Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University 3 , Osaka , 565\u20130871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Kamimura","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine 1 , Osaka University, Osaka, 565\u20130871, Japan"},{"name":"WPI Immunology Frontier Research Center, Osaka University 2 , Osaka , 565\u20130871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaya","family":"Harada","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine 1 , Osaka University, Osaka, 565\u20130871, Japan"},{"name":"WPI Immunology Frontier Research Center, Osaka University 2 , Osaka , 565\u20130871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Oto","sequence":"additional","affiliation":[{"name":"Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Okayama University 4 , Okayama, 700\u20138530 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiyuki","family":"Susaki","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine, Osaka University 5 , Osaka , 565\u20130871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Shintani","sequence":"additional","affiliation":[{"name":"Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University 3 , Osaka , 565\u20130871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayoshi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University 3 , Osaka , 565\u20130871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichiro","family":"Miyoshi","sequence":"additional","affiliation":[{"name":"Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Okayama University 4 , Okayama, 700\u20138530 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiichi","family":"Morii","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine, Osaka University 5 , Osaka , 565\u20130871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshio","family":"Hirano","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine 1 , Osaka University, Osaka, 565\u20130871, Japan"},{"name":"WPI Immunology Frontier Research Center, Osaka University 2 , Osaka , 565\u20130871, Japan"},{"name":"JST-CREST, Osaka University 6 , Osaka, 565\u20130871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Murakami","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine 1 , Osaka University, Osaka, 565\u20130871, Japan"},{"name":"WPI Immunology Frontier Research Center, Osaka University 2 , Osaka , 565\u20130871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meinoshin","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University 3 , Osaka , 565\u20130871, 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