{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:04:44Z","timestamp":1792789484072,"version":"4.5.0"},"reference-count":84,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH-NIAID","award":["R21AI171247"],"award-info":[{"award-number":["R21AI171247"]}]},{"name":"NIH-NIAID","award":["P30 DA013429"],"award-info":[{"award-number":["P30 DA013429"]}]},{"name":"NIH-NIDA","award":["R21AI171247"],"award-info":[{"award-number":["R21AI171247"]}]},{"name":"NIH-NIDA","award":["P30 DA013429"],"award-info":[{"award-number":["P30 DA013429"]}]},{"name":"the Department of Pathology and Laboratory Medicine","award":["R21AI171247"],"award-info":[{"award-number":["R21AI171247"]}]},{"name":"the Department of Pathology and Laboratory Medicine","award":["P30 DA013429"],"award-info":[{"award-number":["P30 DA013429"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Excessive production and response to Type I interferons (IFNs) is a hallmark of systemic lupus erythematosus (SLE). Neuropsychiatric lupus (NPSLE) is a common manifestation of human SLE, with major depression as the most common presentation. Clinical studies have demonstrated that IFN\u03b1 can cause depressive symptoms. We have shown that the kallikrein\u2013kinin system (KKS) [comprised of kallikreins (Klks) and bradykinins] and angiotensin-converting enzyme inhibitors suppressed Type I IFN responses in dendritic cells from lupus-prone mice and human peripheral blood mononuclear cells. Tissue Klk genes are decreased in patients with lupus, and giving exogenous Klk1 ameliorated kidney pathology in mice. We retro-orbitally administered mouse klk1 gene-carrying adenovirus in the Murphy Roths Large lymphoproliferative (MRL\/lpr) lupus-prone mice at early disease onset and analyzed immune responses and depressive-like behavior. Klk1 improved depressive-like behavior, suppressed interferon-responsive genes and neuroinflammation, and reduced plasma IFN\u03b1 levels and proinflammatory cytokines. Klk1 also reduced IFNAR1 and JAK1 protein expression, important upstream molecules in Type I IFN signaling. Klk1 reduced bradykinin B1 receptor expression, which is known to induce proinflammatory response. Together, these findings suggest that Klk1 may be a potential therapeutic candidate to control IFN\u03b1 production\/responses and other inflammatory responses in SLE and NPSLE.<\/jats:p>","DOI":"10.3390\/ijms251810080","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T09:23:04Z","timestamp":1726737784000},"page":"10080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Tissue Kallikrein-1 Suppresses Type I Interferon Responses and Reduces Depressive-Like Behavior in the MRL\/lpr Lupus-Prone Mouse Model"],"prefix":"10.3390","volume":"25","author":[{"given":"Priyanka S.","family":"Bhoj","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Nocito","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5840-6458","authenticated-orcid":false,"given":"Namdev S.","family":"Togre","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malika","family":"Winfield","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody","family":"Lubinsky","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabeeya","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhita","family":"Mogadala","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9180-0884","authenticated-orcid":false,"given":"Alecia","family":"Seliga","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M.","family":"Unterwald","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Persidsky","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Sriram","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1007\/s00296-010-1689-6","article-title":"Psychiatric disorders in patients with systemic lupus erythematosus: Association of anxiety disorder with shorter disease duration","volume":"31","author":"Hawro","year":"2011","journal-title":"Rheumatol. 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