{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:04:46Z","timestamp":1780081486061,"version":"3.54.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The lysosomal enzyme \u03b2-glucuronidase (Gusb) is a key regulator of Lyme-associated and K\/B\u00d7N-induced arthritis severity. The luminal enzymes present in lysosomes provide essential catabolic functions for the homeostatic degradation of a variety of macromolecules. In addition to this essential catabolic function, lysosomes play important roles in the inflammatory response following infection. Secretory lysosomes and related vesicles can participate in the inflammatory response through fusion with the plasma membrane and release of bioactive contents into the extracellular milieu. In this study, we show that GUSB hypomorphism potentiates lysosomal exocytosis following inflammatory stimulation. This leads to elevated secretion of lysosomal contents, including glycosaminoglycans, lysosomal hydrolases, and matrix metalloproteinase 9, a known modulator of Lyme arthritis severity. This mechanistic insight led us to test the efficacy of rapamycin, a drug known to suppress lysosomal exocytosis. Both Lyme and K\/B\u00d7N-associated arthritis were suppressed by this treatment concurrent with reduced lysosomal release.<\/jats:p>","DOI":"10.4049\/jimmunol.1500212","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T02:04:37Z","timestamp":1436839477000},"page":"1647-1656","source":"Crossref","is-referenced-by-count":24,"title":["\u03b2-Glucuronidase, a Regulator of Lyme Arthritis Severity, Modulates Lysosomal Trafficking and MMP-9 Secretion in Response to Inflammatory Stimuli"],"prefix":"10.1093","volume":"195","author":[{"given":"Kenneth K C","family":"Bramwell","sequence":"first","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelton","family":"Mock","sequence":"additional","affiliation":[{"name":"University of Puget Sound , Tacoma, WA 98416"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H","family":"Weis","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Teuscher","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Vermont , Burlington, VT 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis J","family":"Weis","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,15]]},"reference":[{"key":"2025030704041598100_r1","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1001\/jama.2013.278331","article-title":"CDC estimates 300,000 US cases of Lyme disease annually","volume":"310","author":"Kuehn","year":"2013","journal-title":"JAMA"},{"key":"2025030704041598100_r2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nrmicro2714","article-title":"Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes","volume":"10","author":"Radolf","year":"2012","journal-title":"Nat. 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