Janova, Hana

[["dc.bibliographiccitation.firstpage","1083"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1099"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","John, Michael"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Goetz, Alexander A."],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Nau, Roland"],["dc.contributor.author","Borisch, Angela"],["dc.contributor.author","Boutin, Philippe"],["dc.contributor.author","Neumann, Konstantin"],["dc.contributor.author","Bremes, Vanessa"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Waetzig, Vicky"],["dc.contributor.author","Herdegen, Thomas"],["dc.contributor.author","Teismann, Peter"],["dc.contributor.author","Greig, Iain"],["dc.contributor.author","Mueller, Michael"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Mildner, Alexander"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Rotshenker, Shlomo"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T09:56:53Z"],["dc.date.available","2018-11-07T09:56:53Z"],["dc.date.issued","2015"],["dc.description.abstract","The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll-like receptor (TLR) signaling. However, BTK inhibition cannot account for the entire activity spectrum. Effects on TLR-induced proinflammatory cytokine expression in microglia involve AG126 hydrolysis and conversion of its dinitrile side chain to malononitrile (MN). Notably, while liberated MN can subsequently mediate critical AG126 features, full protection in EAE still requires delivery of intact AG126. Its anti-inflammatory potential and especially interference with TLR signaling thus rely on a dual mechanism encompassing BTK and a novel MN-sensitive target. Both principles bear great potential for the therapeutic management of disturbed innate and adaptive immune functions. GLIA 2015;63:1083-1099"],["dc.identifier.doi","10.1002/glia.22803"],["dc.identifier.isi","000353244400011"],["dc.identifier.pmid","25731696"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37056"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1098-1136"],["dc.relation.issn","0894-1491"],["dc.title","Tyrphostin AG126 Exerts Neuroprotection in CNS Inflammation by a Dual Mechanism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","14"],["dc.bibliographiccitation.journal","Journal of Neuroinflammation"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Meister, Tanja"],["dc.contributor.author","Ott, Martina"],["dc.contributor.author","Redlich, Sandra"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Nessler, Stefan"],["dc.contributor.author","Nau, Roland"],["dc.date.accessioned","2018-11-07T09:45:02Z"],["dc.date.available","2018-11-07T09:45:02Z"],["dc.date.issued","2014"],["dc.description.abstract","Background: Prophylaxis with unmethylated cytosine phosphate guanidine (CpG) oligodeoxynucleotides (ODN) protects against several systemic experimental infections. Escherichia coli is a major cause of Gram-negative neonatal bacterial meningitis and also causes meningitis and meningoencephalitis in older and immunocompromised patients. Methods: Wild-type (wt) and Toll-like receptor 9 (TLR9)-deficient mice were rendered neutropenic by intraperitoneal administration of the anti-Ly-6G monoclonal antibody. Immunocompetent and neutropenic mice received intraperitoneal CpG ODN or vehicle 72 h prior to induction of E. coli K1 meningoencephalitis. Results: Pre-treatment with CpG ODN significantly increased survival of neutropenic wt mice from 33% to 75% (P = 0.0003) but did not protect neutropenic TLR9(-/-) mice. The protective effect of CpG ODN was associated with an enhanced production of interleukin (IL)-12/IL-23p40 with sustained increased levels in serum and spleen at least for 17 days after conditioning compared to buffer-treated animals. CpG-treated neutropenic wt mice showed reduced bacterial concentrations and increased recruitment of Ly6C(high)CCR2(+) monocytes in brain and spleen 42 h after infection. The levels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) and interferon gamma (IFN-gamma) in spleen were higher 42 h after infection in CpG-treated compared to buffer-treated neutropenic animals. In immunocompetent mice, prophylaxis with CpG ODN did not significantly increase survival compared to the buffer group (60% vs. 45%, P = 0.2). Conclusions: These findings suggest that systemic administration of CpG ODN may help to prevent bacterial CNS infections in immunocompromised individuals."],["dc.identifier.doi","10.1186/1742-2094-11-14"],["dc.identifier.isi","000333212600001"],["dc.identifier.pmid","24456653"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9757"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34526"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1742-2094"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Intraperitoneal prophylaxis with CpG oligodeoxynucleotides protects neutropenic mice against intracerebral Escherichia coli K1 infection"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Goetz, Alexander A."],["dc.contributor.author","Nau, R."],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Hanisch, U-K"],["dc.date.accessioned","2018-11-07T09:23:23Z"],["dc.date.available","2018-11-07T09:23:23Z"],["dc.date.issued","2013"],["dc.format.extent","S181"],["dc.identifier.isi","000320408400581"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29563"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.conference","11th European Meeting on Glial Cell Function in Health and Disease"],["dc.relation.eventlocation","Berlin, GERMANY"],["dc.relation.issn","0894-1491"],["dc.title","CD14 AS A KEY REGULATOR OF TLR-MEDIATED RESPONSES OF MICROGLIA"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8634"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.lastpage","8647"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Garcia-Agudo, Laura Fernandez"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Sendler, Lea E."],["dc.contributor.author","Arinrad, Sahab"],["dc.contributor.author","Steixner, Agnes A."],["dc.contributor.author","Hassouna, Imam"],["dc.contributor.author","Balmuth, Evan"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Schopf, Nadine"],["dc.contributor.author","Flier, Felicia J."],["dc.contributor.author","Ehrenreich, And Hannelore"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Martens, Henrik"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2022-10-06T13:35:25Z"],["dc.date.available","2022-10-06T13:35:25Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1096/fj.201900337R"],["dc.identifier.eissn","1530-6860"],["dc.identifier.issn","0892-6638"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116091"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-602"],["dc.relation.eissn","1530-6860"],["dc.relation.issn","0892-6638"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.title","Genetically induced brain inflammation by\r\n Cnp\r\n deletion transiently benefits from microglia depletion"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.volume","59"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Kastriti, Maria-Eleni"],["dc.contributor.author","Revelo, Natalia H."],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Borisch, Angela"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T08:51:34Z"],["dc.date.available","2018-11-07T08:51:34Z"],["dc.date.issued","2011"],["dc.format.extent","S148"],["dc.identifier.isi","000294178900582"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21965"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Malden"],["dc.relation.issn","0894-1491"],["dc.title","CD14 AND TRIF GOVERN DISTINCT RESPONSIVENESS AND RESPONSES IN MOUSE MICROGLIAL TLR4 CHALLENGES BY STRUCTURAL VARIANTS OF LPS"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","205"],["dc.bibliographiccitation.journal","Brain Behavior and Immunity"],["dc.bibliographiccitation.lastpage","221"],["dc.bibliographiccitation.volume","48"],["dc.contributor.author","Schaafsma, W."],["dc.contributor.author","Zhang, X."],["dc.contributor.author","van Zomeren, K. C."],["dc.contributor.author","Jacobs, S."],["dc.contributor.author","Georgieva, Petya B."],["dc.contributor.author","Wolf, S. A."],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Saiepour, Nasrin"],["dc.contributor.author","Hanisch, U.-K."],["dc.contributor.author","Meerlo, Peter"],["dc.contributor.author","van den Elsen, Peter J."],["dc.contributor.author","Brouwer, Nieske"],["dc.contributor.author","Boddeke, Hendrikus W. G. M."],["dc.contributor.author","Eggen, Bart J. L."],["dc.date.accessioned","2018-11-07T09:53:59Z"],["dc.date.available","2018-11-07T09:53:59Z"],["dc.date.issued","2015"],["dc.description.abstract","Microglia, the innate immune cells of the central nervous system (CNS), react to endotoxins like bacterial lipopolysaccharides (LPS) with a pronounced inflammatory response. To avoid excess damage to the CNS, the microglia inflammatory response needs to be tightly regulated. Here we report that a single LPS challenge results in a prolonged blunted pro-inflammatory response to a subsequent LPS stimulation, both in primary microglia cultures (100 ng/ml) and in vivo after intraperitoneal (0.25 and 1 mg/kg) or intracere-broventricular (5 mu g) LPS administration. Chromatin immunoprecipitation (ChIP) experiments with primary microglia and microglia acutely isolated from mice showed that LPS preconditioning was accompanied by a reduction in active histone modifications AcH3 and H3K4me3 in the promoters of the IL-10 and TNF-alpha genes. Furthermore, LPS preconditioning resulted in an increase in the amount of repressive histone modification H3K9me2 in the IL-1 beta promoter. ChIP and knock-down experiments showed that NF-kappa B subunit RelB was bound to the IL-1 beta promoter in preconditioned microglia and that RelB is required for the attenuated LPS response. In addition to a suppressed pro-inflammatory response, preconditioned primary microglia displayed enhanced phagocytic activity, increased outward potassium currents and nitric oxide production in response to a second LPS challenge. In vivo, a single i.p. LPS injection resulted in reduced performance in a spatial learning task 4 weeks later, indicating that a single inflammatory episode affected memory formation in these mice. Summarizing, we show that LPS-preconditioned microglia acquire an epigenetically regulated, immune-suppressed phenotype, possibly to prevent excessive damage to the central nervous system in case of recurrent (peripheral) inflammation. (C) 2015 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.bbi.2015.03.013"],["dc.identifier.isi","000358460700023"],["dc.identifier.pmid","25843371"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36442"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","1090-2139"],["dc.relation.issn","0889-1591"],["dc.title","Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","734"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","745"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Arinrad, Sahab"],["dc.contributor.author","Balmuth, Evan"],["dc.contributor.author","Mitjans, Marina"],["dc.contributor.author","Hertel, Johannes"],["dc.contributor.author","Habes, Mohamad"],["dc.contributor.author","Bittner, Robert A."],["dc.contributor.author","Pan, Hong"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Gerwig, Ulrike C."],["dc.contributor.author","Langner, Sönke"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Kittel-Schneider, Sarah"],["dc.contributor.author","Homuth, Georg"],["dc.contributor.author","Davatzikos, Christos"],["dc.contributor.author","Völzke, Henry"],["dc.contributor.author","West, Brian L."],["dc.contributor.author","Reif, Andreas"],["dc.contributor.author","Grabe, Hans Jörgen"],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2020-12-10T18:38:19Z"],["dc.date.available","2020-12-10T18:38:19Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1172/JCI97032"],["dc.identifier.eissn","1558-8238"],["dc.identifier.issn","0021-9738"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77272"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Microglia ablation alleviates myelin-associated catatonic signs in mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","16"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","23"],["dc.bibliographiccitation.volume","252"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Adam, Nina"],["dc.contributor.author","Schuetze, Sandra"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Redlich, Sandra"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Borisch, Angela"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Nau, Roland"],["dc.date.accessioned","2018-11-07T09:03:27Z"],["dc.date.available","2018-11-07T09:03:27Z"],["dc.date.issued","2012"],["dc.description.abstract","Increasing the phagocytic activity of microglia could improve the resistance of immunocompromised patients to CNS infections. We studied the microglial responses upon stimulation with the Nod2 ligand muramyl dipeptide (MDP) alone or in combination with a TLR1/2, 3 or 4 agonist. MDP caused a mild release of NO, but induced neither a significant release of pro-inflammatory cytokines nor an expression of molecules associated with professional antigen presentation. Using the Escherichia coli K1 model, microglial pre-stimulation with MDP enhanced bacterial phagocytosis which was strengthened on TLR-pre-stimulated cells. Dual pre-stimulation of Nod2 and TLR1/2 or 4 caused maximal phagocytosis and intracellular killing. (c) 2012 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jneuroim.2012.07.012"],["dc.identifier.isi","000311132500002"],["dc.identifier.pmid","22889567"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24904"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1872-8421"],["dc.relation.issn","0165-5728"],["dc.title","The nucleotide-binding oligomerization domain-containing-2 ligand muramyl dipeptide enhances phagocytosis and intracellular killing of Escherichia coli K1 by Toll-like receptor agonists in microglial cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","635"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","649"],["dc.bibliographiccitation.volume","64"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Böttcher, Chotima"],["dc.contributor.author","Holtman, Inge R."],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Rossum, Denise van"],["dc.contributor.author","Götz, Alexander"],["dc.contributor.author","Ernst, Anne-Sophie"],["dc.contributor.author","Fritsche, Christin"],["dc.contributor.author","Gertig, Ulla"],["dc.contributor.author","Saiepour, Nasrin"],["dc.contributor.author","Gronke, Konrad"],["dc.contributor.author","Wrzos, Claudia"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Rolfes, Simone"],["dc.contributor.author","Weinstein, Jonathan"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Kopatz, Jens"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Salinas-Riester, Gabriela"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Prinz, Marco"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Eggen, Bart J. L."],["dc.contributor.author","Boddeke, Hendrikus W. G. M."],["dc.contributor.author","Priller, Josef"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2017-09-07T11:45:34Z"],["dc.date.available","2017-09-07T11:45:34Z"],["dc.date.issued","2016"],["dc.description.abstract","Microglia, innate immune cells of the CNS, sense infection and damage through overlapping receptor sets. Toll-like receptor (TLR) 4 recognizes bacterial lipopolysaccharide (LPS) and multiple injury-associated factors. We show that its co-receptor CD14 serves three non-redundant functions in microglia. First, it confers an up to 100-fold higher LPS sensitivity compared to peripheral macrophages to enable efficient proinflammatory cytokine induction. Second, CD14 prevents excessive responses to massive LPS challenges via an interferon β-mediated feedback. Third, CD14 is mandatory for microglial reactions to tissue damage-associated signals. In mice, these functions are essential for balanced CNS responses to bacterial infection, traumatic and ischemic injuries, since CD14 deficiency causes either hypo- or hyperinflammation, insufficient or exaggerated immune cell recruitment or worsened stroke outcomes. While CD14 orchestrates functions of TLR4 and related immune receptors, it is itself regulated by TLR and non-TLR systems to thereby fine-tune microglial damage-sensing capacity upon infectious and non-infectious CNS challenges."],["dc.identifier.doi","10.1002/glia.22955"],["dc.identifier.gro","3150405"],["dc.identifier.pmid","26683584"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7166"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.issn","0894-1491"],["dc.title","CD14 is a key organizer of microglial responses to CNS infection and injury"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1176"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1185"],["dc.bibliographiccitation.volume","65"],["dc.contributor.author","Doering, Christin"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Gertig, Ulla"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Winkler, Anne"],["dc.contributor.author","Saiepour, Nasrin"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Janova, Hana"],["dc.date.accessioned","2018-11-07T10:22:27Z"],["dc.date.available","2018-11-07T10:22:27Z"],["dc.date.issued","2017"],["dc.description.abstract","Microglia as principle innate immune cells of the central nervous system (CNS) are the first line of defense against invading pathogens. They are capable of sensing infections through diverse receptors, such as Toll-like receptor 4 (TLR4). This receptor is best known for its ability to recognize bacterial lipopolysaccharide (LPS), a causative agent of gram-negative sepsis and septic shock. A putative, naturally occurring antagonist of TLR4 derives from the photosynthetic bacterium Rhodobacter sphaeroides. However, the antagonistic potential of R. sphaeroides LPS (Rs-LPS) is no universal feature, since several studies suggested agonistic rather than antagonistic actions of this molecule depending on the investigated mammalian species. Here we show the agonistic versus antagonistic potential of Rs-LPS in primary mouse microglia. We demonstrate that Rs-LPS efficiently induces the release of cytokines and chemokines, which depends on TLR4, MyD88, and TRIF, but not CD14. Furthermore, Rs-LPS is able to regulate the phagocytic capacity of microglia as agonist, while it antagonizes Re-LPS-induced MHC I expression. Finally, to our knowledge, we are the first to provide in vivo evidence for an agonistic potential of Rs-LPS, as it efficiently triggers the recruitment of peripheral immune cells to the endotoxin-challenged CNS. Together, our results argue for a versatile and complex organization of the microglial TLR4 system, which specifically translates exogenous signals into cellular functions. Importantly, as demonstrated here for microglia, the antagonistic potential of Rs-LPS needs to be considered with caution, as reactions to Rs-LPS not only differ by cell type, but even by function within one cell type."],["dc.description.sponsorship","German Research Council (DFG) [SFB/TRR43, FOR1336]"],["dc.identifier.doi","10.1002/glia.23151"],["dc.identifier.isi","000401345400011"],["dc.identifier.pmid","28471051"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42277"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley"],["dc.relation.issn","1098-1136"],["dc.relation.issn","0894-1491"],["dc.title","A presumed antagonistic LPS identifies distinct functional organization of TLR4 in mouse microglia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]