{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:54:13Z","timestamp":1787241253772,"version":"build-2736575974"},"reference-count":62,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"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":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    To elucidate the role of reactive oxygen species (ROS) in arthritis and to identify targets of arthritis treatment in conditions with different levels of oxidant stress.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    Through establishing an arthritis model by injecting arthritogenic serum into wild-type and NADPH oxidase 2 (NOX2)-deficient mice, we found that arthritis had a neutrophilic infiltrate and was more severe in\n                    <jats:italic toggle=\"yes\">\n                      Ncf1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice, a mouse strain lacking the expression of the NCF1\/p47\n                    <jats:sup>phox<\/jats:sup>\n                    component of NOX2. The levels of interleukin-1\u03b2 (IL-1\u03b2) and IL-6 in inflamed joints were higher in\n                    <jats:italic toggle=\"yes\">\n                      Ncf1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    than in controls. Antagonists of tumor necrosis factor-\u03b1 (TNF\u03b1) and IL-1\u03b2 were equally effective in suppressing arthritis in wild-type mice, while IL-1\u03b2 blockade was more effective than TNF\u03b1 blockade in\n                    <jats:italic toggle=\"yes\">\n                      Ncf1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice. A treatment of caspase inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a cathepsin inhibitor alone, suppressed arthritic severity in the wild-type mice, while a treatment of cathepsin inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a caspase inhibitor alone, were effective in treating\n                    <jats:italic toggle=\"yes\">\n                      Ncf1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Consistently, cathepsin B was found to proteolytically process pro-IL-1\u03b2 to its active form and this activity was suppressed by ROS.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    This novel mechanism of a redox-mediated immune regulation of arthritis through leukocyte-produced ROS is important for devising an optimal treatment for patients with different levels of tissue ROS.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    Our results suggest that ROS act as a negative feedback to constrain IL-1\u03b2-mediated inflammation, accounting for the more severe arthritis in the absence of NOX2.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    23, 973\u2013984.\n                  <\/jats:p>","DOI":"10.1089\/ars.2014.6136","type":"journal-article","created":{"date-parts":[[2015,4,13]],"date-time":"2015-04-13T12:07:57Z","timestamp":1428926877000},"page":"973-984","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Redox Regulation of Pro-IL-1\u03b2 Processing May Contribute to the Increased Severity of Serum-Induced Arthritis in NOX2-Deficient Mice"],"prefix":"10.1177","volume":"23","author":[{"given":"Ya-Fang","family":"Huang","sequence":"first","affiliation":[{"name":"National Cheng Kung University College of Medicine","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Chi","family":"Lo","sequence":"additional","affiliation":[{"name":"National Cheng Kung University College of Medicine","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Liang","family":"Yen","sequence":"additional","affiliation":[{"name":"National Cheng Kung University College of Medicine","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Andrija","family":"Nigrovic","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital"},{"name":"Boston Children's Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chen","family":"Chao","sequence":"additional","affiliation":[{"name":"National Cheng Kung University College of Medicine","place":["Taiwan"]},{"name":"Taichung Veteran General Hospital","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Zhi","family":"Wang","sequence":"additional","affiliation":[{"name":"National Cheng Kung University College of Medicine","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Chengkang","family":"Hsu","sequence":"additional","affiliation":[{"name":"National Cheng Kung University College of Medicine","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yau-Sheng","family":"Tsai","sequence":"additional","affiliation":[{"name":"National Cheng Kung University College of Medicine","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Chang","family":"Shieh","sequence":"additional","affiliation":[{"name":"National Cheng Kung University College of Medicine","place":["Taiwan"]},{"name":"National Cheng Kung University Hospital","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,10,20]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2007.02.002"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00046-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2001.2642"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24601"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301672"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.173"},{"key":"e_1_3_3_8_2","first-page":"1103","article-title":"Effects of anakinra monotherapy on joint damage in patients with rheumatoid arthritis. Extension of a 24-week randomized, placebo-controlled trial","volume":"31","author":"Bresnihan B","year":"2004","unstructured":"Bresnihan B, , Newmark R, , Robbins S, , and Genant HK. Effects of anakinra monotherapy on joint damage in patients with rheumatoid arthritis. Extension of a 24-week randomized, placebo-controlled trial. J Rheumatol, 31: 1103\u20131111, 2004.","journal-title":"J Rheumatol"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11419"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2999"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2007.03321.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2009.12.013"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-05-1822"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.07.050"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1297-319X(01)00335-9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01661"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000036"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24959"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg332"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1447"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.06.037"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.3.1431"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403831101"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3625"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21755"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.03.031"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.393"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199104000-00008"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000016"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/JOM.0b013e318282d310"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1996.0048"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2012.727991"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-265892"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012645108"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737556"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.12.008"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1039\/c2mt20156a"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199912)42:12<2517::AID-ANR3>3.0.CO;2-W"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04515"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-402-5_20"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-004-0679-8"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1446"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1058"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4013"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050473"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00398.2012"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1159\/000136357"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.05.035"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-008-0119-2"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9425"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.205138"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-200005000-00004"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.078014"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20130497"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1222"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds516"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-402-5_18"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1601"},{"key":"e_1_3_3_59_2","first-page":"225","article-title":"Interleukin 6 inhibition\u2014RA and beyond","volume":"69","author":"Woodrick RS","year":"2011","unstructured":"Woodrick RS, and Ruderman EM. Interleukin 6 inhibition\u2014RA and beyond. Bull NYU Hosp Jt Dis, 69: 225\u2013229, 2011.","journal-title":"Bull NYU Hosp Jt Dis"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12034"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00514"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1831"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4278fje"}],"container-title":["Antioxidants &amp; Redox Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2014.6136","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/ars.2014.6136","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2014.6136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:53:08Z","timestamp":1777377188000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/ars.2014.6136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10]]},"references-count":62,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1089\/ars.2014.6136"],"URL":"https:\/\/doi.org\/10.1089\/ars.2014.6136","relation":{},"ISSN":["1523-0864","1557-7716"],"issn-type":[{"value":"1523-0864","type":"print"},{"value":"1557-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10]]}}}