{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:50:26Z","timestamp":1785408626863,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-060"],"award-info":[{"award-number":["2021-I2M-1-060"]}]},{"DOI":"10.13039\/501100004829","name":"Department of Science and Technology of Sichuan Province","doi-asserted-by":"publisher","award":["2023NSFSC0714"],"award-info":[{"award-number":["2023NSFSC0714"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2023NSFSC0714"],"award-info":[{"award-number":["2023NSFSC0714"]}],"id":[{"id":"https:\/\/ror.org\/04323m874","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal barrier disruption and dysregulated immune responses. While Intravenous Immunoglobulin (IVIG) is widely used for its immunomodulatory effects in various autoimmune conditions, its specific therapeutic mechanisms and molecular targets in colitis remain to be fully elucidated. Objective: To elucidate the therapeutic mechanisms of IVIG in dextran sodium sulfate (DSS)-induced colitis, with a focus on pyroptosis regulation via the NOD-like receptor (NLR) signaling pathway. Methods: Colitis was induced in mice via DSS administration. IVIG was administered intravenously during disease progression. Colon tissues underwent proteomic profiling, and key targets (GBP5, NLRP3, Pro-Caspase-1, GSDMD) were validated by Western blotting (WB), while interleukin (IL)-1\u03b2 and IL-18 levels were quantified via ELISA. Results: IVIG significantly attenuated weight loss, Disease Activity Index (DAI) scores, colon shortening, and histopathological damage. Proteomics analysis identified 172 differentially expressed proteins between DSS and DSS + IVIG groups, with pronounced downregulation of GBP5 and NLR pathway components. IVIG suppressed GBP5\/NLRP3\/CASP1 activation, reduced GSDMD cleavage, and significantly decreased IL-1\u03b2 production (while showing a decreasing trend for IL-18). Conclusions: IVIG ameliorates colitis by inhibiting the GBP5\/NLRP3\/CASP1-mediated pyroptosis pathway, highlighting its potential as a targeted therapy for ulcerative colitis.<\/jats:p>","DOI":"10.3390\/ph19060972","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intravenous Immunoglobulin Reveals a Novel Protective Mechanism: Targeting the GBP5-Driven Pyroptosis Axis in Experimental Colitis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5199-4916","authenticated-orcid":false,"given":"Qian","family":"Long","sequence":"first","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"},{"name":"West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4467-785X","authenticated-orcid":false,"given":"Tong","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5764-7660","authenticated-orcid":false,"given":"Zongkui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changqing","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-7191","authenticated-orcid":false,"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41572-020-0205-x","article-title":"Ulcerative colitis","volume":"6","author":"Kobayashi","year":"2020","journal-title":"Nat. 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