{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T07:47:08Z","timestamp":1791100028424,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,5,25]]},"abstract":"<jats:p>\n                    In healthy monocytes, Toll-like receptor (TLR) engagement induces production of reactive oxygen species (ROS), followed by an antioxidant response involved in IL-1\u03b2 processing and secretion. Markers of the antioxidant response include intracellular thioredoxin and extracellular release of reduced cysteine. Cryopyrin-associated periodic syndromes (CAPS) are autoinflammatory diseases in which Nod-like receptor family pyrin domain\u2013containing 3 (\n                    <jats:italic>NLRP3)<\/jats:italic>\n                    gene mutations lead to increased IL-1\u03b2 secretion. We show in a large cohort of patients that IL-1\u03b2 secretion by CAPS monocytes is much faster than that by healthy monocytes. This accelerated kinetics is caused by alterations in the basal redox state, as well as in the redox response to TLR triggering displayed by CAPS monocytes. Indeed, unstimulated CAPS monocytes are under a mild oxidative stress, with elevated levels of both ROS and antioxidants. The redox response to LPS is quickened, with early generation of the reducing conditions favoring IL-1\u03b2 processing and secretion, and then rapidly exhausted. Therefore, secretion of IL-1\u03b2 is accelerated, but reaches a plateau much earlier than in healthy controls. Pharmacologic inhibition of the redox response hinders IL-1\u03b2 release, confirming the functional link between redox impairment and altered kinetics of secretion. Monocytes from patients with juvenile idiopathic arthritis display normal kinetics of redox response and IL-1\u03b2 secretion, excluding a role of chronic inflammation in the alterations observed in CAPS. We conclude that preexisting redox alterations distinct from CAPS monocytes anticipate the pathogen-associated molecular pattern molecule\u2013induced generation of the reducing environment favorable to inflammasome activation and IL-1\u03b2 secretion.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1000779107","type":"journal-article","created":{"date-parts":[[2010,5,5]],"date-time":"2010-05-05T22:53:50Z","timestamp":1273100030000},"page":"9789-9794","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":135,"title":["Altered redox state of monocytes from cryopyrin-associated periodic syndromes causes accelerated IL-1\u03b2 secretion"],"prefix":"10.1073","volume":"107","author":[{"given":"Sara","family":"Tassi","sequence":"first","affiliation":[{"name":"Cell Biology Unit, National Cancer Research Institute, 16132 Genoa, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Carta","sequence":"additional","affiliation":[{"name":"Cell Biology Unit, National Cancer Research Institute, 16132 Genoa, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Delfino","sequence":"additional","affiliation":[{"name":"Cell Biology Unit, National Cancer Research Institute, 16132 Genoa, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Caorsi","sequence":"additional","affiliation":[{"name":"Second Division of Pediatrics, \u201cG. Gaslini\u201d Institute and Department of Pediatrics, University of Genoa, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Martini","sequence":"additional","affiliation":[{"name":"Second Division of Pediatrics, \u201cG. Gaslini\u201d Institute and Department of Pediatrics, University of Genoa, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Gattorno","sequence":"additional","affiliation":[{"name":"Second Division of Pediatrics, \u201cG. Gaslini\u201d Institute and Department of Pediatrics, University of Genoa, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rubartelli","sequence":"additional","affiliation":[{"name":"Cell Biology Unit, National Cancer Research Institute, 16132 Genoa, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,5,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132612"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132715"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709684105"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608083200"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1156995"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.12.8410"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1633"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900578"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210796"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.17.11455"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.9.25"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.226"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022630299"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838439"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902204106"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141627"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-07-2531"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00046-9"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10688"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055137"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22842"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20494"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082481"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23437"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-094201"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.3.751"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0682-09.2009"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.03.071"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel269"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1008598"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050473"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2966"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1000779107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:50:45Z","timestamp":1649789445000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1000779107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5,5]]},"references-count":33,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2010,5,25]]}},"alternative-id":["10.1073\/pnas.1000779107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1000779107","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5,5]]},"assertion":[{"value":"2010-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}