{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:45:35Z","timestamp":1791859535773,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T00:00:00Z","timestamp":1472083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T00:00:00Z","timestamp":1472083200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"NIH"},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["UL1-TR-000042"],"award-info":[{"award-number":["UL1-TR-000042"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Rochester and National Institute of General Medical Sciences","award":["GM-081772"],"award-info":[{"award-number":["GM-081772"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH (Rochester Autoimmunity Center of Excellence)","award":["U19-AI-563262"],"award-info":[{"award-number":["U19-AI-563262"]}],"id":[{"id":"https:\/\/ror.org\/02y9qjz38","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["P01-AI-078907"],"award-info":[{"award-number":["P01-AI-078907"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases Accelerated Medicines Partnership award","award":["1UH2-AR-067690"],"award-info":[{"award-number":["1UH2-AR-067690"]}],"id":[{"id":"https:\/\/ror.org\/006zn3t30","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Bertha and Louis Weinstein Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Despite considerable advances in the understanding of systemic lupus erythematosus (SLE), there is still an urgent need for new and more targeted treatment approaches. We previously demonstrated that small\u2010molecule blockade of G protein \u03b2\u03b3 subunit (G\u03b2\u03b3) signaling inhibits acute inflammation through inhibition of chemokine receptor signal transduction. We undertook this study to determine whether inhibition of G\u03b2\u03b3 signaling ameliorates disease in a mouse model of SLE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Lupus\u2010prone (NZB \u00d7 NZW)F1 female mice were prophylactically or therapeutically treated with the small\u2010molecule G\u03b2\u03b3 inhibitor gallein. Tissue samples were analyzed by flow cytometry and immunohistochemistry. The development and extent of nephritis were assessed by monitoring proteinuria and by immunohistochemical analysis. Serum immunoglobulin levels were measured by enzyme\u2010linked immunosorbent assay, and total IgG and anti\u2013double\u2010stranded DNA (anti\u2010dsDNA) antibody\u2013secreting cells were measured by enzyme\u2010linked immunospot assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Gallein inhibited accumulation of T cells and germinal center (GC) B cells in the spleen. Both prophylactic and therapeutic treatment reduced GC size, decreased antibody\u2010secreting cell production in the spleen, and markedly decreased accumulation of autoreactive anti\u2010dsDNA antibody\u2013secreting cells in kidneys. Gallein also reduced immune complex deposition in kidneys. Finally, gallein treatment dramatically inhibited kidney inflammation, prevented glomerular damage, and decreased proteinuria. Mechanistically, gallein inhibited immune cell migration and signaling in response to chemokines in vitro, which suggests that its mechanisms of action in vivo are inhibition of migration of immune cells to sites of inflammation and inhibition of immune cell maturation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, these data demonstrate the potential use of gallein or novel inhibitors of G\u03b2\u03b3 signaling in SLE treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.39673","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T03:25:20Z","timestamp":1458357920000},"page":"2244-2256","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of G Protein \u03b2\u03b3 Subunit Signaling Abrogates Nephritis in Lupus\u2010Prone Mice"],"prefix":"10.1002","volume":"68","author":[{"given":"Javier","family":"Rangel\u2010Moreno","sequence":"first","affiliation":[{"name":"University of Rochester School of Medicine Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesi Y.","family":"To","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Owen","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce I.","family":"Goldman","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan V.","family":"Smrcka","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine Rochester New 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