{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:22:07Z","timestamp":1791354127972,"version":"4.3.1"},"reference-count":47,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2009,11,30]],"date-time":"2009-11-30T00:00:00Z","timestamp":1259539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Interleukin\u20101\u03b2 (IL\u20101\u03b2) is a key cytokine linked to the pathogenesis of acute arthritis. Caspase 1, neutrophil elastase, and chymase all process proIL\u20101\u03b2 to its biologically active form. This study was undertaken to examine the potential contributions of each of these proteases in experimental models of inflammatory arthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Caspase 1\u2013deficient (\n                      <jats:italic>Casp1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) and wild\u2010type (WT) mice were tested for their response to arthritogenic K\/BxN serum transfer for induction of arthritis or injection of monosodium urate monohydrate (MSU) crystals for induction of peritonitis. All mice were prophylactically treated with inhibitors of neutrophil elastase or chymase. Arthritic paws were tested for the presence of IL\u20101\u03b2 protein by enzyme\u2010linked immunosorbent assay and Western blotting. Neutrophils and mast cells from WT and mutant mice were tested for their ability to secrete IL\u20101\u03b2 after in vitro stimulation, in the presence of protease inhibitors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Casp1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and WT mice developed paw swelling to the same extent in the K\/BxN serum transfer\u2013induced arthritis model. MSU crystal injection into\n                      <jats:italic>Casp1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice also resulted in neutrophil influx and production of measurable peritoneal IL\u20101\u03b2 protein. Both of these responses were attenuated with neutrophil elastase inhibitors. K\/BxN serum transfer\u2013induced arthritis was also reduced by treatment with a chymase inhibitor.\n                      <jats:italic>Casp1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      neutrophils and mast cells, when exposed to MSU crystals, secreted similar amounts of IL\u20101\u03b2 protein upon in vitro stimulation with lipopolysaccharide, albeit at lower levels than that secreted by WT cells. Elastase and chymase inhibitors reduced the amount of IL\u20101\u03b2 released by these cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The production of IL\u20101\u03b2 by neutrophils and mast cells is not exclusively dependent on caspase 1, and other proteases can compensate for the loss of caspase 1 in vivo. These pathways might therefore compromise the caspase 1\u2013targeted therapies in neutrophil\u2010predominant arthritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.24959","type":"journal-article","created":{"date-parts":[[2009,11,30]],"date-time":"2009-11-30T13:13:25Z","timestamp":1259586805000},"page":"3642-3650","source":"Crossref","is-referenced-by-count":282,"title":["Caspase 1\u2013independent activation of interleukin\u20101\u03b2 in neutrophil\u2010predominant inflammation"],"prefix":"10.1002","volume":"60","author":[{"given":"Monica","family":"Guma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Ronacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Liu\u2010Bryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Takai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Karin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maripat","family":"Corr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,11,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000185500.11080.91"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132612"},{"key":"e_1_2_6_4_2","doi-asserted-by":"crossref","first-page":"9437","DOI":"10.1016\/S0021-9258(19)76559-4","article-title":"Generation 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