{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:10:54Z","timestamp":1790968254392,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T00:00:00Z","timestamp":1141171200000},"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":[[2006,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Group B streptococcus (GBS) is the major cause of sepsis in newborn infants. In vitro, inactivated GBS stimulates macrophages to produce inflammatory proteins via the TLR adapter protein MyD88. Furthermore, inflammatory cytokine release in response to GBS greatly exceeds that following stimulation with pneumococci. In this study, we attempted to unravel signaling events that are involved in GBS-, but not Streptococcus pneumoniae-stimulated phagocytes to identify molecular targets for adjunctive sepsis therapy. We found that inactivated GBS and S. pneumoniae differed in the activation of the MAPK JNK, but not I\u03baB kinase. Furthermore, JNK was essential for the transcriptional activation of inflammatory cytokine genes in response to GBS. Inhibition of JNK by the anthrapyrazolone SP600125 abrogated GBS-induced cytokine formation via an AP-1- and NF-\u03baB-dependent mechanism without impairing antibacterial properties such as phagocytosis of GBS and the formation of intracellular oxidative species. In contrast, inhibition of the MAPK p38 impaired both antibacterial processes. In a neonatal mouse model of GBS sepsis SP600125 inhibited the inflammatory response and improved survival. In conclusion, JNK plays a major role in the inflammatory, but not in the direct antibacterial response to inactivated GBS, and may thus serve as a rational target for an adjunctive GBS sepsis therapy.<\/jats:p>","DOI":"10.4049\/jimmunol.176.5.3181","type":"journal-article","created":{"date-parts":[[2014,4,23]],"date-time":"2014-04-23T19:49:01Z","timestamp":1398282541000},"page":"3181-3188","source":"Crossref","is-referenced-by-count":41,"title":["c-Jun Kinase Is a Critical Signaling Molecule in a Neonatal Model of Group B Streptococcal Sepsis"],"prefix":"10.1093","volume":"176","author":[{"given":"Sybille","family":"Kenzel","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital, Albert-Ludwigs University , Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiseppe","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Dipartimento di Patologia e Microbiologia Sperimentale, Universita\u0300 di Messina , Messina ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Malley","sequence":"additional","affiliation":[{"name":"Channing Laboratory, Brigham and Women\u2019s Hospital, and Departments of Medicine, Microbiology, and Molecular Genetics, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiseppe","family":"Teti","sequence":"additional","affiliation":[{"name":"Dipartimento di Patologia e Microbiologia Sperimentale, Universita\u0300 di Messina , Messina ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas T","family":"Golenbock","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Henneke","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital, Albert-Ludwigs University , Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,3,1]]},"reference":[{"key":"2026020211371960300_R1","first-page":"201","volume-title":"Lancet Infect. 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