{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:48:03Z","timestamp":1790743683243,"version":"4.1.0"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,10,4]],"date-time":"2016-10-04T00:00:00Z","timestamp":1475539200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,10,4]],"date-time":"2016-10-04T00:00:00Z","timestamp":1475539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The endotoxin lipopolysaccharide (LPS) promotes sepsis, but bacterial peptides also promote inflammation leading to sepsis. We found, intraperitoneal administration of live or heat inactivated<jats:italic>E. coli<\/jats:italic>JE5505 lacking the abundant outer membrane protein, Braun lipoprotein (BLP), was less toxic than<jats:italic>E. coli<\/jats:italic>DH5\u03b1 possessing BLP in Swiss albino mice. Injection of BLP free of LPS purified from<jats:italic>E. coli<\/jats:italic>DH5\u03b1 induced massive infiltration of leukocytes in lungs and liver. BLP activated human polymorphonuclear cells (PMNs)<jats:italic>ex vivo<\/jats:italic>to adhere to denatured collagen in serum and polymyxin B independent fashion, a property distinct from LPS. Both LPS and BLP stimulated the synthesis of platelet activating factor (PAF), a potent lipid mediator, in human PMNs. In mouse macrophage cell line, RAW264.7, while both BLP and LPS similarly upregulated TNF-\u03b1 and IL-1\u03b2 mRNA; BLP was more potent in inducing cyclooxygenase-2 (COX-2) mRNA and protein expression. Peritoneal macrophages from TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice significantly reduced the production of TNF-\u03b1 in response to BLP in contrast to macrophages from wild type mice. We conclude, BLP acting through TLR2, is a potent inducer of inflammation with a response profile both common and distinct from LPS. Hence, BLP mediated pathway may also be considered as an effective target against sepsis.<\/jats:p>","DOI":"10.1038\/srep34666","type":"journal-article","created":{"date-parts":[[2016,10,4]],"date-time":"2016-10-04T12:11:04Z","timestamp":1475583064000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Escherichia coli Braun Lipoprotein (BLP) exhibits endotoxemia \u2013 like pathology in Swiss albino mice"],"prefix":"10.1038","volume":"6","author":[{"given":"Chikkamenahalli Lakshminarayana","family":"Lakshmikanth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shancy Petsel","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash Kundadka","family":"Kudva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calivarathan","family":"Latchoumycandane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puttaraju Srikanta Murthy","family":"Yashaswini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mosale Seetharam","family":"Sumanth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassiano F.","family":"Goncalves-de-Albuquerque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana R.","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridevi Annapurna","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo C.","family":"Castro-Faria-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep Kumble","family":"Prabhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"McIntyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopal Kedihithlu","family":"Marathe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,4]]},"reference":[{"key":"BFsrep34666_CR1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer, M. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315, 801\u2013810 (2016).","journal-title":"JAMA"},{"key":"BFsrep34666_CR2","doi-asserted-by":"crossref","first-page":"671087","DOI":"10.1155\/2014\/671087","volume":"2014","author":"R de Pablo","year":"2014","unstructured":"de Pablo, R., Monserrat, J., Prieto, A. & Alvarez-Mon, M. Role of circulating lymphocytes in patients with sepsis. Biomed Res Int 2014, 671087 (2014).","journal-title":"Biomed Res Int"},{"key":"BFsrep34666_CR3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1757-7241-20-41","volume":"20","author":"SM Perman","year":"2012","unstructured":"Perman, S. M., Goyal, M. & Gaieski, D. F. Initial emergency department diagnosis and management of adult patients with severe sepsis and septic shock. Scand J Trauma Resusc Emerg Med 20, 41 (2012).","journal-title":"Scand J Trauma Resusc Emerg Med"},{"key":"BFsrep34666_CR4","doi-asserted-by":"crossref","unstructured":"Chaudhry, N. & Duggal, A. K. Sepsis Associated Encephalopathy. Advances in Medicine 2014 (2014).","DOI":"10.1155\/2014\/762320"},{"key":"BFsrep34666_CR5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.molmed.2014.01.007","volume":"20","author":"JC Marshall","year":"2014","unstructured":"Marshall, J. C. Why have clinical trials in sepsis failed? Trends Mol Med 20, 195\u2013203 (2014).","journal-title":"Trends Mol Med"},{"key":"BFsrep34666_CR6","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1189\/jlb.0912437","volume":"93","author":"M Aziz","year":"2013","unstructured":"Aziz, M., Jacob, A., Yang, W. L., Matsuda, A. & Wang, P. Current trends in inflammatory and immunomodulatory mediators in sepsis. J Leukoc Biol 93, 329\u2013342 (2013).","journal-title":"J Leukoc Biol"},{"key":"BFsrep34666_CR7","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1128\/CMR.00046-08","volume":"22","author":"TH Mogensen","year":"2009","unstructured":"Mogensen, T. H. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev 22, 240\u2013273, Table of Contents (2009).","journal-title":"Clin Microbiol Rev"},{"key":"BFsrep34666_CR8","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1128\/CMR.16.3.379-414.2003","volume":"16","author":"ES Van Amersfoort","year":"2003","unstructured":"Van Amersfoort, E. S., Van Berkel, T. J. & Kuiper, J. Receptors, mediators, and mechanisms involved in bacterial sepsis and septic shock. Clin Microbiol Rev 16, 379\u2013414 (2003).","journal-title":"Clin Microbiol Rev"},{"key":"BFsrep34666_CR9","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1186\/1364-8535-17-1001","volume":"17","author":"N de Prost","year":"2013","unstructured":"de Prost, N., Razazi, K. & Brun-Buisson, C. Unrevealing culture-negative severe sepsis. Crit Care 17, 1001 (2013).","journal-title":"Crit Care"},{"key":"BFsrep34666_CR10","doi-asserted-by":"crossref","first-page":"R202","DOI":"10.1186\/cc12896","volume":"17","author":"J Phua","year":"2013","unstructured":"Phua, J. et al. Characteristics and outcomes of culture-negative versus culture-positive severe sepsis. Crit Care 17, R202 (2013).","journal-title":"Crit Care"},{"key":"BFsrep34666_CR11","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1097\/00024382-200013020-00004","volume":"13","author":"DG Remick","year":"2000","unstructured":"Remick, D. G., Newcomb, D. E., Bolgos, G. L. & Call, D. R. Comparison of the mortality and inflammatory response of two models of sepsis: lipopolysaccharide vs. cecal ligation and puncture. Shock 13, 110\u2013116 (2000).","journal-title":"Shock"},{"key":"BFsrep34666_CR12","doi-asserted-by":"crossref","unstructured":"Nair, S. R., Geetha, C. & Mohanan, P. Analysis of IL-1\u03b2 Release from Cryopreserved Pooled Lymphocytes in Response to Lipopolysaccharide and Lipoteichoic Acid. BioMed research international 2013 (2013).","DOI":"10.1155\/2013\/689642"},{"key":"BFsrep34666_CR13","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1021\/bm400356m","volume":"14","author":"AP Le Brun","year":"2013","unstructured":"Le Brun, A. P. et al. Structural characterization of a model Gram-negative bacterial surface using lipopolysaccharides from rough strains of Escherichia coli. Biomacromolecules 14, 2014\u20132022 (2013).","journal-title":"Biomacromolecules"},{"key":"BFsrep34666_CR14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fcimb.2013.00003","volume":"3","author":"N Maeshima","year":"2013","unstructured":"Maeshima, N. & Fernandez, R. C. Recognition of lipid A variants by the TLR4-MD-2 receptor complex. Front Cell Infect Microbiol 3, 3 (2013).","journal-title":"Front Cell Infect Microbiol"},{"key":"BFsrep34666_CR15","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3389\/fimmu.2014.00461","volume":"5","author":"T Kawasaki","year":"2014","unstructured":"Kawasaki, T. & Kawai, T. Toll-like receptor signaling pathways. Front Immunol 5, 461 (2014).","journal-title":"Front Immunol"},{"key":"BFsrep34666_CR16","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.2402637","volume":"249","author":"RR Schumann","year":"1990","unstructured":"Schumann, R. R. et al. Structure and function of lipopolysaccharide binding protein. Science 249, 1429\u20131431 (1990).","journal-title":"Science"},{"key":"BFsrep34666_CR17","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1084\/jem.179.1.269","volume":"179","author":"E Hailman","year":"1994","unstructured":"Hailman, E. et al. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med 179, 269\u2013277 (1994).","journal-title":"J Exp Med"},{"key":"BFsrep34666_CR18","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","volume":"42","author":"YC Lu","year":"2008","unstructured":"Lu, Y. C., Yeh, W. C. & Ohashi, P. S. LPS\/TLR4 signal transduction pathway. Cytokine 42, 145\u2013151 (2008).","journal-title":"Cytokine"},{"key":"BFsrep34666_CR19","doi-asserted-by":"crossref","first-page":"R698","DOI":"10.1152\/ajpregu.00039.2002","volume":"283","author":"RA Frost","year":"2002","unstructured":"Frost, R. A., Nystrom, G. J. & Lang, C. H. Lipopolysaccharide regulates proinflammatory cytokine expression in mouse myoblasts and skeletal muscle. Am J Physiol Regul Integr Comp Physiol 283, R698\u2013709 (2002).","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"BFsrep34666_CR20","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1096\/fj.04-2691fje","volume":"19","author":"MA Birrell","year":"2005","unstructured":"Birrell, M. A. et al. Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-kappaB-independent mechanism. FASEB J 19, 840\u2013841 (2005).","journal-title":"FASEB J"},{"key":"BFsrep34666_CR21","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1093\/infdis\/158.2.312","volume":"158","author":"T Calandra","year":"1988","unstructured":"Calandra, T., Glauser, M. P., Schellekens, J. & Verhoef, J. Treatment of gram-negative septic shock with human IgG antibody to Escherichia coli J5: a prospective, double-blind, randomized trial. J Infect Dis 158, 312\u2013319 (1988).","journal-title":"J Infect Dis"},{"key":"BFsrep34666_CR22","doi-asserted-by":"crossref","unstructured":"The French National Registry of HA-1A (Centoxin) in septic shock. A cohort study of 600 patients. The National Committee for the Evaluation of Centoxin. Arch Intern Med 154, 2484\u20132491 (1994).","DOI":"10.1001\/archinte.154.21.2484"},{"key":"BFsrep34666_CR23","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1001\/jama.2013.2194","volume":"309","author":"SM Opal","year":"2013","unstructured":"Opal, S. M. et al. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA 309, 1154\u20131162 (2013).","journal-title":"JAMA"},{"key":"BFsrep34666_CR24","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1097\/CCM.0b013e3181e7c5c9","volume":"38","author":"TW Rice","year":"2010","unstructured":"Rice, T. W. et al. A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis. Crit Care Med 38, 1685\u20131694 (2010).","journal-title":"Crit Care Med"},{"key":"BFsrep34666_CR25","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/S0140-6736(05)60602-2","volume":"351","author":"E Abraham","year":"1998","unstructured":"Abraham, E. et al. Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group. Lancet 351, 929\u2013933 (1998).","journal-title":"Lancet"},{"key":"BFsrep34666_CR26","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1097\/00003246-200103000-00006","volume":"29","author":"E Abraham","year":"2001","unstructured":"Abraham, E. et al. Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients. Crit Care Med 29, 503\u2013510 (2001).","journal-title":"Crit Care Med"},{"key":"BFsrep34666_CR27","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1097\/00003246-199707000-00010","volume":"25","author":"SM Opal","year":"1997","unstructured":"Opal, S. M. et al. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group. Crit Care Med 25, 1115\u20131124 (1997).","journal-title":"Crit Care Med"},{"key":"BFsrep34666_CR28","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1128\/iai.59.6.2110-2115.1991","volume":"59","author":"MA Freudenberg","year":"1991","unstructured":"Freudenberg, M. A. & Galanos, C. Tumor necrosis factor alpha mediates lethal activity of killed gram-negative and gram-positive bacteria in D-galactosamine-treated mice. Infect Immun 59, 2110\u20132115 (1991).","journal-title":"Infect Immun"},{"key":"BFsrep34666_CR29","doi-asserted-by":"crossref","first-page":"618","DOI":"10.4049\/jimmunol.165.2.618","volume":"165","author":"M Hirschfeld","year":"2000","unstructured":"Hirschfeld, M., Ma, Y., Weis, J. H., Vogel, S. N. & Weis, J. J. Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J Immunol 165, 618\u2013622 (2000).","journal-title":"J Immunol"},{"key":"BFsrep34666_CR30","doi-asserted-by":"crossref","first-page":"5231","DOI":"10.4049\/jimmunol.167.9.5231","volume":"167","author":"PO Neilsen","year":"2001","unstructured":"Neilsen, P. O., Zimmerman, G. A. & McIntyre, T. M. Escherichia coli Braun lipoprotein induces a lipopolysaccharide-like endotoxic response from primary human endothelial cells. J Immunol 167, 5231\u20135239 (2001).","journal-title":"J Immunol"},{"key":"BFsrep34666_CR31","doi-asserted-by":"crossref","first-page":"5978","DOI":"10.1128\/JB.186.18.5978-5987.2004","volume":"186","author":"W Vollmer","year":"2004","unstructured":"Vollmer, W. & Holtje, J. V. The architecture of the murein (peptidoglycan) in gram-negative bacteria: vertical scaffold or horizontal layer(s)? J Bacteriol 186, 5978\u20135987 (2004).","journal-title":"J Bacteriol"},{"key":"BFsrep34666_CR32","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1128\/JB.188.8.2761-2773.2006","volume":"188","author":"MM Babu","year":"2006","unstructured":"Babu, M. M. et al. A database of bacterial lipoproteins (DOLOP) with functional assignments to predicted lipoproteins. J Bacteriol 188, 2761\u20132773 (2006).","journal-title":"J Bacteriol"},{"key":"BFsrep34666_CR33","doi-asserted-by":"crossref","first-page":"10552","DOI":"10.1021\/jf8023722","volume":"56","author":"H Tamta","year":"2008","unstructured":"Tamta, H. et al. Variability in in vitro macrophage activation by commercially diverse bulk echinacea plant material is predominantly due to bacterial lipoproteins and lipopolysaccharides. J Agric Food Chem 56, 10552\u201310556 (2008).","journal-title":"J Agric Food Chem"},{"key":"BFsrep34666_CR34","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.4049\/jimmunol.180.5.3436","volume":"180","author":"M Bastian","year":"2008","unstructured":"Bastian, M., Braun, T., Bruns, H., Rollinghoff, M. & Stenger, S. Mycobacterial lipopeptides elicit CD4+ CTLs in Mycobacterium tuberculosis-infected humans. J Immunol 180, 3436\u20133446 (2008).","journal-title":"J Immunol"},{"key":"BFsrep34666_CR35","doi-asserted-by":"crossref","first-page":"e10250","DOI":"10.1371\/journal.pone.0010250","volume":"5","author":"N Dietrich","year":"2010","unstructured":"Dietrich, N., Lienenklaus, S., Weiss, S. & Gekara, N. O. Murine toll-like receptor 2 activation induces type I interferon responses from endolysosomal compartments. PLoS One 5, e10250 (2010).","journal-title":"PLoS One"},{"key":"BFsrep34666_CR36","doi-asserted-by":"crossref","first-page":"e19583","DOI":"10.1371\/journal.pone.0019583","volume":"6","author":"X Du","year":"2011","unstructured":"Du, X. et al. Systemic stimulation of TLR2 impairs neonatal mouse brain development. PLoS One 6, e19583 (2011).","journal-title":"PLoS One"},{"key":"BFsrep34666_CR37","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1128\/jb.127.1.555-563.1976","volume":"127","author":"S Inoyye","year":"1976","unstructured":"Inoyye, S. et al. Lipoprotein from the outer membrane of Escherichia coli: purification, paracrystallization, and some properties of its free form. J Bacteriol 127, 555\u2013563 (1976).","journal-title":"J Bacteriol"},{"key":"BFsrep34666_CR38","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.intimp.2010.08.012","volume":"10","author":"V Kumar","year":"2010","unstructured":"Kumar, V. & Sharma, A. Neutrophils: Cinderella of innate immune system. Int Immunopharmacol 10, 1325\u20131334 (2010).","journal-title":"Int Immunopharmacol"},{"key":"BFsrep34666_CR39","doi-asserted-by":"crossref","first-page":"949157","DOI":"10.1155\/2012\/949157","volume":"2012","author":"E Liaskou","year":"2012","unstructured":"Liaskou, E., Wilson, D. V. & Oo, Y. H. Innate immune cells in liver inflammation. Mediators Inflamm 2012, 949157 (2012).","journal-title":"Mediators Inflamm"},{"key":"BFsrep34666_CR40","doi-asserted-by":"crossref","first-page":"33161","DOI":"10.1074\/jbc.M305321200","volume":"278","author":"J Watanabe","year":"2003","unstructured":"Watanabe, J. et al. Endotoxins stimulate neutrophil adhesion followed by synthesis and release of platelet-activating factor in microparticles. J Biol Chem 278, 33161\u201333168 (2003).","journal-title":"J Biol Chem"},{"key":"BFsrep34666_CR41","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1146\/annurev.biochem.69.1.419","volume":"69","author":"SM Prescott","year":"2000","unstructured":"Prescott, S. M., Zimmerman, G. A., Stafforini, D. M. & McIntyre, T. M. Platelet-activating factor and related lipid mediators. Annu Rev Biochem 69, 419\u2013445 (2000).","journal-title":"Annu Rev Biochem"},{"key":"BFsrep34666_CR42","doi-asserted-by":"crossref","first-page":"17381","DOI":"10.1016\/S0021-9258(18)38167-5","volume":"265","author":"SM Prescott","year":"1990","unstructured":"Prescott, S. M., Zimmerman, G. A. & McIntyre, T. M. Platelet-activating factor. J Biol Chem 265, 17381\u201317384 (1990).","journal-title":"J Biol Chem"},{"key":"BFsrep34666_CR43","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1194\/jlr.R045492","volume":"55","author":"GK Marathe","year":"2014","unstructured":"Marathe, G. K. et al. To hydrolyze or not to hydrolyze: the dilemma of platelet-activating factor acetylhydrolase. J Lipid Res 55, 1847\u20131854 (2014).","journal-title":"J Lipid Res"},{"key":"BFsrep34666_CR44","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S0022-2275(20)40190-7","volume":"5","author":"WR Morrison","year":"1964","unstructured":"Morrison, W. R. & Smith, L. M. Preparation of Fatty Acid Methyl Esters and Dimethylacetals from Lipids with Boron Fluoride\u2013Methanol. J Lipid Res 5, 600\u2013608 (1964).","journal-title":"J Lipid Res"},{"key":"BFsrep34666_CR45","doi-asserted-by":"crossref","first-page":"L1289","DOI":"10.1152\/ajplung.2000.278.6.L1289","volume":"278","author":"MM Ndengele","year":"2000","unstructured":"Ndengele, M. M., Bellone, C. J., Lechner, A. J. & Matuschak, G. M. Brief hypoxia differentially regulates LPS-induced IL-1beta and TNF-alpha gene transcription in RAW 264.7 cells. Am J Physiol Lung Cell Mol Physiol 278, L1289\u20131296 (2000).","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"BFsrep34666_CR46","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1476-511X-11-76","volume":"11","author":"AA Qureshi","year":"2012","unstructured":"Qureshi, A. A. et al. Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macrophages by resveratrol, a potent proteasome inhibitor. Lipids Health Dis 11, 76 (2012).","journal-title":"Lipids Health Dis"},{"key":"BFsrep34666_CR47","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/mnfr.200600226","volume":"51","author":"MM Rafi","year":"2007","unstructured":"Rafi, M. M., Yadav, P. N. & Rossi, A. O. Glucosamine inhibits LPS-induced COX-2 and iNOS expression in mouse macrophage cells (RAW 264.7) by inhibition of p38-MAP kinase and transcription factor NF-kappaB. Mol Nutr Food Res 51, 587\u2013593 (2007).","journal-title":"Mol Nutr Food Res"},{"key":"BFsrep34666_CR48","doi-asserted-by":"crossref","first-page":"6454","DOI":"10.1074\/jbc.M111.327874","volume":"287","author":"M Font-Nieves","year":"2012","unstructured":"Font-Nieves, M. et al. Induction of COX-2 enzyme and down-regulation of COX-1 expression by lipopolysaccharide (LPS) control prostaglandin E2 production in astrocytes. J Biol Chem 287, 6454\u20136468 (2012).","journal-title":"J Biol Chem"},{"key":"BFsrep34666_CR49","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1432-1033.1975.tb20996.x","volume":"60","author":"B Jann","year":"1975","unstructured":"Jann, B., Reske, K. & Jann, K. Heterogeneity of lipopolysaccharides. Analysis of polysaccharide chain lengths by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Eur J Biochem 60, 239\u2013246 (1975).","journal-title":"Eur J Biochem"},{"key":"BFsrep34666_CR50","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/sj.bjp.0702747","volume":"128","author":"Y Endo","year":"1999","unstructured":"Endo, Y. et al. Enhancement by galactosamine of lipopolysaccharide(LPS)-induced tumour necrosis factor production and lethality: its suppression by LPS pretreatment. Br J Pharmacol 128, 5\u201312 (1999).","journal-title":"Br J Pharmacol"},{"key":"BFsrep34666_CR51","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.yexmp.2007.03.004","volume":"83","author":"VR Sunil","year":"2007","unstructured":"Sunil, V. R. et al. Acute endotoxemia is associated with upregulation of lipocalin 24p3\/Lcn2 in lung and liver. Exp Mol Pathol 83, 177\u2013187 (2007).","journal-title":"Exp Mol Pathol"},{"key":"BFsrep34666_CR52","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1128\/IAI.05043-11","volume":"79","author":"JL Johnson","year":"2011","unstructured":"Johnson, J. L., Hong, H., Monfregola, J. & Catz, S. D. Increased survival and reduced neutrophil infiltration of the liver in Rab27a- but not Munc13-4-deficient mice in lipopolysaccharide-induced systemic inflammation. Infect Immun 79, 3607\u20133618 (2011).","journal-title":"Infect Immun"},{"key":"BFsrep34666_CR53","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S1665-2681(19)31751-X","volume":"8","author":"A Taye","year":"2009","unstructured":"Taye, A., El-Moselhy, M. A., Hassan, M. K., Ibrahim, H. M. & Mohammed, A. F. Hepatoprotective effect of pentoxifylline against D-galactosamine-induced hepatotoxicity in rats. Ann Hepatol 8, 364\u2013370 (2009).","journal-title":"Ann Hepatol"},{"key":"BFsrep34666_CR54","doi-asserted-by":"crossref","first-page":"73","DOI":"10.33549\/physiolres.930275","volume":"52","author":"R Ferencikova","year":"2003","unstructured":"Ferencikova, R., Cervinkova, Z. & Drahota, Z. Hepatotoxic effect of D-galactosamine and protective role of lipid emulsion. Physiol Res 52, 73\u201378 (2003).","journal-title":"Physiol Res"},{"key":"BFsrep34666_CR55","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1128\/iai.59.8.2609-2614.1991","volume":"59","author":"AK Franks","year":"1991","unstructured":"Franks, A. K., Kujawa, K. I. & Yaffe, L. J. Experimental elimination of tumor necrosis factor in low-dose endotoxin models has variable effects on survival. Infect Immun 59, 2609\u20132614 (1991).","journal-title":"Infect Immun"},{"key":"BFsrep34666_CR56","doi-asserted-by":"crossref","first-page":"R1202","DOI":"10.1152\/ajpregu.2000.278.5.R1202","volume":"278","author":"M Nowak","year":"2000","unstructured":"Nowak, M. et al. LPS-induced liver injury in D-galactosamine-sensitized mice requires secreted TNF-alpha and the TNF-p55 receptor. Am J Physiol Regul Integr Comp Physiol 278, R1202\u20131209 (2000).","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"BFsrep34666_CR57","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/sj.ki.5000038","volume":"69","author":"V Savransky","year":"2006","unstructured":"Savransky, V. et al. Role of the T-cell receptor in kidney ischemia-reperfusion injury. Kidney Int 69, 233\u2013238 (2006).","journal-title":"Kidney Int"},{"key":"BFsrep34666_CR58","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1172\/JCI64181","volume":"123","author":"J Klesney-Tait","year":"2013","unstructured":"Klesney-Tait, J. et al. Transepithelial migration of neutrophils into the lung requires TREM-1. J Clin Invest 123, 138\u2013149 (2013).","journal-title":"J Clin Invest"},{"key":"BFsrep34666_CR59","doi-asserted-by":"crossref","first-page":"26630","DOI":"10.1074\/jbc.M112.341255","volume":"287","author":"S Dey","year":"2012","unstructured":"Dey, S. et al. Impact of intravascular hemolysis in malaria on liver dysfunction: involvement of hepatic free heme overload, NF-kappaB activation, and neutrophil infiltration. J Biol Chem 287, 26630\u201326646 (2012).","journal-title":"J Biol Chem"},{"key":"BFsrep34666_CR60","first-page":"31397","volume":"2007","author":"AN Kurt","year":"2007","unstructured":"Kurt, A. N. et al. Serum IL-1beta, IL-6, IL-8, and TNF-alpha levels in early diagnosis and management of neonatal sepsis. Mediators Inflamm 2007, 31397 (2007).","journal-title":"Mediators Inflamm"},{"key":"BFsrep34666_CR61","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/jlb.55.6.711","volume":"55","author":"SR Smith","year":"1994","unstructured":"Smith, S. R., Terminelli, C., Kenworthy-Bott, L., Calzetta, A. & Donkin, J. The cooperative effects of TNF-alpha and IFN-gamma are determining factors in the ability of IL-10 to protect mice from lethal endotoxemia. J Leukoc Biol 55, 711\u2013718 (1994).","journal-title":"J Leukoc Biol"},{"key":"BFsrep34666_CR62","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1128\/iai.61.9.3843-3853.1993","volume":"61","author":"Y Ma","year":"1993","unstructured":"Ma, Y. & Weis, J. J. Borrelia burgdorferi outer surface lipoproteins OspA and OspB possess B-cell mitogenic and cytokine-stimulatory properties. Infect Immun 61, 3843\u20133853 (1993).","journal-title":"Infect Immun"},{"key":"BFsrep34666_CR63","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.micpath.2007.09.005","volume":"44","author":"T Liu","year":"2008","unstructured":"Liu, T. et al. Immunological responses against Salmonella enterica serovar Typhimurium Braun lipoprotein and lipid A mutant strains in Swiss-Webster mice: potential use as live-attenuated vaccines. Microb Pathog 44, 224\u2013237 (2008).","journal-title":"Microb Pathog"},{"key":"BFsrep34666_CR64","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1128\/IAI.01529-07","volume":"76","author":"J Sha","year":"2008","unstructured":"Sha, J. et al. Braun lipoprotein (Lpp) contributes to virulence of yersiniae: potential role of Lpp in inducing bubonic and pneumonic plague. Infect Immun 76, 1390\u20131409 (2008).","journal-title":"Infect Immun"},{"key":"BFsrep34666_CR65","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.1099\/mic.0.029124-0","volume":"155","author":"SL Agar","year":"2009","unstructured":"Agar, S. L. et al. Deletion of Braun lipoprotein gene (lpp) and curing of plasmid pPCP1 dramatically alter the virulence of Yersinia pestis CO92 in a mouse model of pneumonic plague. Microbiology 155, 3247\u20133259 (2009).","journal-title":"Microbiology"},{"key":"BFsrep34666_CR66","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.micpath.2009.09.002","volume":"48","author":"T Liu","year":"2010","unstructured":"Liu, T., Agar, S. L., Sha, J. & Chopra, A. K. Deletion of Braun lipoprotein gene (lpp) attenuates Yersinia pestis KIM\/D27 strain: role of Lpp in modulating host immune response, NF-kappaB activation and cell death. Microb Pathog 48, 42\u201352 (2010).","journal-title":"Microb Pathog"},{"key":"BFsrep34666_CR67","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/cgt.2009.58","volume":"17","author":"T Liu","year":"2010","unstructured":"Liu, T. & Chopra, A. K. An enteric pathogen Salmonella enterica serovar Typhimurium suppresses tumor growth by downregulating CD44high and CD4T regulatory (Treg) cell expression in mice: the critical role of lipopolysaccharide and Braun lipoprotein in modulating tumor growth. Cancer Gene Ther 17, 97\u2013108 (2010).","journal-title":"Cancer Gene Ther"},{"key":"BFsrep34666_CR68","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1128\/IAI.01067-12","volume":"81","author":"J Sha","year":"2013","unstructured":"Sha, J. et al. Deletion of the Braun lipoprotein-encoding gene and altering the function of lipopolysaccharide attenuate the plague bacterium. Infect Immun 81, 815\u2013828 (2013).","journal-title":"Infect Immun"},{"key":"BFsrep34666_CR69","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1128\/IAI.01595-13","volume":"82","author":"CJ van Lier","year":"2014","unstructured":"van Lier, C. J. et al. Deletion of Braun lipoprotein and plasminogen-activating protease-encoding genes attenuates Yersinia pestis in mouse models of bubonic and pneumonic plague. Infect Immun 82, 2485\u20132503 (2014).","journal-title":"Infect Immun"},{"key":"BFsrep34666_CR70","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.smim.2003.10.003","volume":"16","author":"K Takeda","year":"2004","unstructured":"Takeda, K. & Akira, S. TLR signaling pathways. Semin Immunol 16, 3\u20139 (2004).","journal-title":"Semin Immunol"},{"key":"BFsrep34666_CR71","doi-asserted-by":"crossref","first-page":"e13889","DOI":"10.1371\/journal.pone.0013889","volume":"5","author":"M Barrenschee","year":"2010","unstructured":"Barrenschee, M., Lex, D. & Uhlig, S. Effects of the TLR2 agonists MALP-2 and Pam3Cys in isolated mouse lungs. PLoS One 5, e13889 (2010).","journal-title":"PLoS One"},{"key":"BFsrep34666_CR72","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s00011-016-0937-y","volume":"65","author":"CL Lakshmikanth","year":"2016","unstructured":"Lakshmikanth, C. L. et al. Sepsis \u2013 In search of cure. Inflamm Res 65, 587\u2013602 (2016).","journal-title":"Inflamm Res"},{"key":"BFsrep34666_CR73","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1073\/pnas.74.4.1417","volume":"74","author":"Y Hirota","year":"1977","unstructured":"Hirota, Y., Suzuki, H., Nishimura, Y. & Yasuda, S. On the process of cellular division in Escherichia coli: a mutant of E. coli lacking a murein-lipoprotein. Proc Natl Acad Sci USA 74, 1417\u20131420 (1977).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep34666_CR74","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nature10072","volume":"474","author":"LE Sander","year":"2011","unstructured":"Sander, L. E. et al. Sensing prokaryotic mRNA signifies microbial viability and promotes immunity. Nature 474, 385\u2013389 (2011).","journal-title":"Nature"},{"key":"BFsrep34666_CR75","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1128\/jb.127.1.555-563.1976","volume":"127","author":"S Inoyye","year":"1976","unstructured":"Inoyye, S. et al. Lipoprotein from the outer membrane of Escherichia coli: purification, paracrystallization, and some properties of its free form. J Bacteriol 127, 555\u2013563 (1976).","journal-title":"J Bacteriol"},{"key":"BFsrep34666_CR76","first-page":"123","volume":"27","author":"CL Lakshmikanth","year":"2015","unstructured":"Lakshmikanth, C. L. et al. Interference of phenol during quantification of a bacterial lipoprotein. Biokemistri 27, 123\u2013128 (2015).","journal-title":"Biokemistri"},{"key":"BFsrep34666_CR77","doi-asserted-by":"crossref","first-page":"28395","DOI":"10.1074\/jbc.274.40.28395","volume":"274","author":"GK Marathe","year":"1999","unstructured":"Marathe, G. K. et al. Inflammatory platelet-activating factor-like phospholipids in oxidized low density lipoproteins are fragmented alkyl phosphatidylcholines. J Biol Chem 274, 28395\u201328404 (1999).","journal-title":"J Biol Chem"},{"key":"BFsrep34666_CR78","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/y59-099","volume":"37","author":"EG Bligh","year":"1959","unstructured":"Bligh, E. G. & Dyer, W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37, 911\u2013917 (1959).","journal-title":"Can J Biochem Physiol"},{"key":"BFsrep34666_CR79","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1172\/JCI118288","volume":"96","author":"JM Heery","year":"1995","unstructured":"Heery, J. M. et al. Oxidatively modified LDL contains phospholipids with platelet-activating factor-like activity and stimulates the growth of smooth muscle cells. J Clin Invest 96, 2322\u20132330 (1995).","journal-title":"J Clin Invest"},{"key":"BFsrep34666_CR80","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.3945\/jn.111.141176","volume":"141","author":"SM Nelson","year":"2011","unstructured":"Nelson, S. M., Lei, X. & Prabhu, K. S. Selenium levels affect the IL-4-induced expression of alternative activation markers in murine macrophages. J Nutr 141, 1754\u20131761 (2011).","journal-title":"J Nutr"},{"key":"BFsrep34666_CR81","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/1523-1747.ep12506462","volume":"78","author":"PP Bradley","year":"1982","unstructured":"Bradley, P. P., Priebat, D. A., Christensen, R. D. & Rothstein, G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78, 206\u2013209 (1982).","journal-title":"J Invest Dermatol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep34666.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep34666","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep34666.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T09:46:26Z","timestamp":1692524786000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep34666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,4]]},"references-count":81,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,16]]}},"alternative-id":["BFsrep34666"],"URL":"https:\/\/doi.org\/10.1038\/srep34666","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,4]]},"assertion":[{"value":"1 April 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"34666"}}