{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:14:15Z","timestamp":1791400455692,"version":"4.3.3"},"reference-count":60,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2003,8,11]],"date-time":"2003-08-11T00:00:00Z","timestamp":1060560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2003,8,11]],"date-time":"2003-08-11T00:00:00Z","timestamp":1060560000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Brain invasion by\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    , the agent of Lyme disease, results in an inflammatory and neurodegenerative disorder called neuroborreliosis. In humans, neuroborreliosis has been correlated with enhanced concentration of glial fibrillary acidic protein in the cerebrospinal fluid, a sign of astrogliosis. Rhesus monkeys infected by us with\n                    <jats:italic>B.\u2004burgdorferi<\/jats:italic>\n                    showed evidence of astrogliosis, namely astrocyte proliferation and apoptosis. We formulated the hypothesis that astrogliosis could be caused by spirochetal lipoproteins. We established primary cultures of rhesus monkey astrocytes and stimulated the cells with recombinant lipidated outer surface protein\u2004A (L\u2010OspA), a model\n                    <jats:italic>B.\u2004burgdorferi<\/jats:italic>\n                    lipoprotein, and tripalmitoyl\u2010S\u2010glyceryl\u2010Cys\u2010Ser\u2010Lys\n                    <jats:sub>4<\/jats:sub>\n                    \u2010OH (Pam\n                    <jats:sub>3<\/jats:sub>\n                    Cys), a synthetic lipopeptide that mimics the structure of the lipoprotein lipid moiety. L\u2010OspA elicited not only astrocyte proliferation but also apoptosis, two features observed during astrogliosis. Astrocytes produced both IL\u20106 and TNF\u2010\u03b1 in response to L\u2010OspA and Pam\n                    <jats:sub>3<\/jats:sub>\n                    Cys. Proliferation induced by L\u2010OspA was diminished in the presence of an excess of anti\u2010IL\u20106 antibody, and apoptosis induced by this lipoprotein was completely suppressed with anti\u2010TNF\u2010\u03b1 antibody. Hence, IL\u20106 contributes to, and TNF\u2010\u03b1 determines, astrocyte proliferation and apoptosis, respectively, as elicited by lipoproteins. Our results provide proof of the principle that spirochetal lipoproteins could be key virulence factors in Lyme neuroborreliosis, and that astrogliosis might contribute to neuroborreliosis pathogenesis.\n                  <\/jats:p>","DOI":"10.1002\/eji.200323872","type":"journal-article","created":{"date-parts":[[2003,8,21]],"date-time":"2003-08-21T16:41:17Z","timestamp":1061484077000},"page":"2539-2550","source":"Crossref","is-referenced-by-count":61,"title":["Pathogenesis of Lyme neuroborreliosis:\n                    <i>Borrelia burgdorferi<\/i>\n                    lipoproteins induce both proliferation and apoptosis in rhesus monkey astrocytes"],"prefix":"10.1002","volume":"33","author":[{"given":"Geeta","family":"Ramesh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alida L.","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Donald","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vida A.","family":"Dennis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara L.","family":"Lasater","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario T.","family":"Philipp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,8,11]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1040908"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.37.5.749"},{"key":"e_1_2_7_3_2","article-title":"Aspects of the pathogenesis of neuroborreliosis. In Schutzer, S. (Ed.) 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