{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:06:48Z","timestamp":1760242008096,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T00:00:00Z","timestamp":1542585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Microsomal prostaglandin E synthetase-1 (mPGES-1) is an inducible terminal enzyme for the production of prostaglandin E2 (PGE2). In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mPGES-1 is induced in vascular endothelial cells (VECs) around inflammatory foci and facilitates inflammation, demyelination, and paralysis. Therefore, we investigated the role of CD31-positive VECs in mPGES-1-mediated EAE aggravation using immunohistochemical analysis and imaging of wild-type (wt) and mPGES-1-deficient (mPGES-1\u2212\/\u2212) mice. We demonstrated that EAE induction facilitated vascularity in inflammatory lesions in the spinal cord, and this was significantly higher in wt mice than in mPGES-1\u2212\/\u2212 mice. In addition, endothelial interleukin-1\u03b2 (IL-1\u03b2) production was significantly higher in wt mice than in mPGES-1\u2212\/\u2212 mice. Moreover, endothelial PGE2 receptors (E-prostanoid (EP) receptors EP1\u20134) were expressed after EAE induction, and IL-1\u03b2 was induced in EP receptor-positive VECs. Furthermore, IL-1 receptor 1 expression on VECs was increased upon EAE induction. Thus, increased vascularity is one mechanism involved in EAE aggravation induced by mPGES-1. Furthermore, mPGES-1 facilitated the autocrine function of VECs upon EP receptor induction and IL-1\u03b2 production, modulating mPGES-1 induction in EAE.<\/jats:p>","DOI":"10.3390\/ijms19113647","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T11:23:27Z","timestamp":1542799407000},"page":"3647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Endothelial Microsomal Prostaglandin E Synthetase-1 Upregulates Vascularity and Endothelial Interleukin-1\u03b2 in Deteriorative Progression of Experimental Autoimmune Encephalomyelitis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0877-5698","authenticated-orcid":false,"given":"Takako","family":"Takemiya","sequence":"first","affiliation":[{"name":"Medical Research Institute, Tokyo Women\u2019s Medical University, Tokyo 162-8666, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marumi","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Tokyo Women\u2019s Medical University, Tokyo 162-8666, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chisen","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo 114-0033, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1523\/JNEUROSCI.21-08-02669.2001","article-title":"Coexpression of microsomal-type prostaglandin E synthase with cyclooxygenase-2 in brain endothelial cells of rats during endotoxin-induced fever","volume":"21","author":"Yamagata","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/jnr.22195","article-title":"Endothelial microsomal prostaglandin E synthase-1 exacerbates neuronal loss induced by kainate","volume":"88","author":"Takemiya","year":"2010","journal-title":"J. Neurosci. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jneuroim.2003.12.021","article-title":"Inflammatory cell expression of cyclooxygenase-2 in the multiple sclerosis lesion","volume":"149","author":"Rose","year":"2004","journal-title":"J. Neuroimmunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S0165-5728(98)00257-4","article-title":"Cyclooxygenases-1 and -2 are differentially localized to microglia and endothelium in rat EAE and glioma","volume":"95","author":"Deininger","year":"1999","journal-title":"J. Neuroimmunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1002\/eji.1830250723","article-title":"A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H-2b mice: Fine specificity and T cell receptor V\u03b2 expression of encephalitogenic T cells","volume":"25","author":"Mendel","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jneuroim.2007.06.016","article-title":"MP4- and MOG:35-55-induced EAE in C57BL\/6 mice differentially targets brain, spinal cord and cerebellum","volume":"189","author":"Kuerten","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0162-3109(84)90059-6","article-title":"Prostaglandin and thromboxane levels in central nervous system tissues from rats during the induction and development of experimental allergic encephalomyelitis (EAE)","volume":"7","author":"Bolton","year":"1984","journal-title":"Immunopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1084\/jem.20050665","article-title":"Cytosolic phospholipase A2 alpha-deficient mice are resistant to experimental autoimmune encephalomyelitis","volume":"202","author":"Marusic","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"21807","DOI":"10.1073\/pnas.0906891106","article-title":"Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis","volume":"106","author":"Kihara","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.neuint.2012.12.007","article-title":"Microsomal prostaglandin E synthase-1 aggravates inflammation and demyelination in a mouse model of multiple sclerosis","volume":"62","author":"Takeuchi","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1093\/brain\/awl170","article-title":"Selective COX-2 inhibitor celecoxib prevents experimental autoimmune encephalomyelitis through COX-2-independent pathway","volume":"129","author":"Miyamoto","year":"2006","journal-title":"Brain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s10875-006-8787-y","article-title":"COX-2 inhibitors modulate IL-12 signaling through JAK-STAT pathway leading to Th1 response in experimental allergic encephalomyelitis","volume":"26","author":"Muthian","year":"2006","journal-title":"J. Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jneuroim.2007.03.012","article-title":"COX-2 inhibitors ameliorate experimental autoimmune encephalomyelitis through modulating IFN-gamma and IL-10 production by inhibiting T-bet expression","volume":"186","author":"Ni","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0165-5728(95)00108-E","article-title":"Protective effect of the interleukin-1 receptor antagonist (IL-1RA) on experimental allergic encephalomyelitis in rats","volume":"61","author":"Martin","year":"1995","journal-title":"J. Neuroimmunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1006\/clim.2000.4851","article-title":"The induction of EAE is only partially dependent on TNF receptor signaling but requires the IL-1 type I receptor","volume":"95","author":"Schiffenbauer","year":"2000","journal-title":"Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Takemiya, T., Takeuchi, C., and Kawakami, M. (2017). Microsomal prostaglandin E synthase-1 facilitates an intercellular interaction between CD4(+) T cells through IL-1beta autocrine function in experimental autoimmune encephalomyelitis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122758"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/glia.10108","article-title":"Matrix Metalloproteinases in Neuroinflammation","volume":"39","author":"Rosenberg","year":"2002","journal-title":"Glia"},{"key":"ref_18","first-page":"R1203","article-title":"Gelatinase B modulates selective opening of the blood-brain barrier during inflammation","volume":"274","author":"Rosenberg","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1139\/o96-082","article-title":"The roles of adhesion molecules and proteinases in lymphocyte transendothelial migration","volume":"74","author":"Madri","year":"1996","journal-title":"Biochem. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Seabrook, T.J., Littlewood-Evans, A., Brinkmann, V., Pollinger, B., Schnell, C., and Hiestand, P.C. (2010). Angiogenesis is present in experimental autoimmune encephalomyelitis and pro-angiogenic factors are increased in multiple sclerosis lesions. J. Neuroinflamm., 7.","DOI":"10.1186\/1742-2094-7-95"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1093\/brain\/awm118","article-title":"Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy","volume":"130","author":"Rigau","year":"2007","journal-title":"Brain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.arcmed.2014.11.013","article-title":"Role of the blood-brain barrier in multiple sclerosis","volume":"45","author":"Ortiz","year":"2014","journal-title":"Arch. Med. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jneuroim.2009.01.009","article-title":"VEGF and angiogenesis in acute and chronic MOG(35-55) peptide induced EAE","volume":"209","author":"Roscoe","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1038\/nm.2943","article-title":"Angiogenesis induced by CNS inflammation promotes neuronal remodeling through vessel-derived prostacyclin","volume":"18","author":"Muramatsu","year":"2012","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1038\/nm.2990","article-title":"Not just a rush of blood to the head","volume":"18","author":"Brumm","year":"2012","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1212\/WNL.36.12.1587","article-title":"Prostaglandin release in multiple sclerosis: Correlation with disease activity","volume":"36","author":"Donaldson","year":"1986","journal-title":"Neurology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1002\/jcla.1860040403","article-title":"Prostaglandin production in chronic progressive multiple sclerosis","volume":"4","author":"Aberg","year":"1990","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7220","DOI":"10.1073\/pnas.96.13.7220","article-title":"Identification of human prostaglandin E synthase: A microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target","volume":"96","author":"Jakobsson","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1006\/bbrc.2002.6531","article-title":"Identification and characterization of a novel type of membrane-associated prostaglandin E synthase","volume":"291","author":"Tanikawa","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"32775","DOI":"10.1074\/jbc.M003504200","article-title":"Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis","volume":"275","author":"Tanioka","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"32783","DOI":"10.1074\/jbc.M003505200","article-title":"Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2","volume":"275","author":"Murakami","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.neulet.2011.09.005","article-title":"Function of prostaglandin E2 EP receptors in the acute outcome of rodent hypoxic ischemic encephalopathy","volume":"504","author":"Taniguchi","year":"2011","journal-title":"Neurosci. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Frankowski, J.C., DeMars, K.M., Ahmad, A.S., Hawkins, K.E., Yang, C., Leclerc, J.L., Dore, S., and Candelario-Jalil, E. (2015). Detrimental role of the EP1 prostanoid receptor in blood-brain barrier damage following experimental ischemic stroke. Sci. Rep., 5.","DOI":"10.1038\/srep17956"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4879","DOI":"10.1111\/bph.12815","article-title":"Multiple roles of the PGE2 -EP receptor signal in vascular permeability","volume":"171","author":"Omori","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/jnc.13117","article-title":"Exogenous arachidonic acid mediates permeability of human brain microvessel endothelial cells through prostaglandin E2 activation of EP3 and EP4 receptors","volume":"135","author":"Dalvi","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4362","DOI":"10.1172\/JCI46279","article-title":"Signaling via the prostaglandin E(2) receptor EP4 exerts neuronal and vascular protection in a mouse model of cerebral ischemia","volume":"121","author":"Liang","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1084\/jem.20151437","article-title":"Myeloid cell transmigration across the CNS vasculature triggers IL-1beta-driven neuroinflammation during autoimmune encephalomyelitis in mice","volume":"213","author":"Levesque","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8153","DOI":"10.1523\/JNEUROSCI.20-21-08153.2000","article-title":"Interleukin-1beta-induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: A magnetic resonance study","volume":"20","author":"Blamire","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.4049\/jimmunol.177.8.5574","article-title":"IL-1\u03b2 regulates blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program","volume":"177","author":"Argaw","year":"2006","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3389\/fneur.2015.00180","article-title":"The role of astrocytes in multiple sclerosis progression","volume":"6","author":"Correale","year":"2015","journal-title":"Front. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wang, Y., Jin, S., Sonobe, Y., Cheng, Y., Horiuchi, H., Parajuli, B., Kawanokuchi, J., Mizuno, T., Takeuchi, H., and Suzumura, A. (2014). Interleukin-1beta induces blood-brain barrier disruption by downregulating sonic hedgehog in astrocytes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110024"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jneuroim.2014.11.023","article-title":"Chronic systemic IL-1beta exacerbates central neuroinflammation independently of the blood-brain barrier integrity","volume":"278","author":"Murta","year":"2015","journal-title":"J. Neuroimmunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1002\/glia.22711","article-title":"In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed","volume":"62","author":"Vainchtein","year":"2014","journal-title":"Glia"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dumas, A., Amiable, N., de Rivero Vaccari, J.P., Chae, J.J., Keane, R.W., Lacroix, S., and Vallieres, L. (2014). The inflammasome pyrin contributes to pertussis toxin-induced IL-1beta synthesis, neutrophil intravascular crawling and autoimmune encephalomyelitis. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004150"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/ni1507","article-title":"Multiple sclerosis: A complicated picture of autoimmunity","volume":"8","author":"McFarland","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/ni.3389","article-title":"T cell-intrinsic ASC critically promotes T(h)17-mediated experimental autoimmune encephalomyelitis","volume":"17","author":"Martin","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1365-2567.2006.02376.x","article-title":"E prostanoid 2 (EP2)\/EP4-mediated suppression of antigen-specific human T-cell responses by prostaglandin E2","volume":"118","author":"Okano","year":"2006","journal-title":"Immunology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.vetimm.2014.05.003","article-title":"Prostaglandin E(2) down-regulates the expression of CD25 on bovine T cells, and this effect is mediated through the EP4 receptor","volume":"160","author":"Maslanka","year":"2014","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/icb.2015.62","article-title":"Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors","volume":"94","author":"Sreeramkumar","year":"2016","journal-title":"Immunol. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1002\/jnr.20597","article-title":"Heterogeneous expression and regulation of hippocampal prostaglandin E2 receptors","volume":"81","author":"Zhu","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0006-8993(96)00575-6","article-title":"Endothelial cells of the rat brain vasculature express cyclooxygenase-2 mRNA in response to systemic interleukin-1 beta: A possible site of prostaglandin synthesis responsible for fever","volume":"733","author":"Cao","year":"1996","journal-title":"Brain Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/(SICI)1097-4547(19991115)58:4<593::AID-JNR12>3.0.CO;2-4","article-title":"Interleukin-1\u03b2 activates expression of cyclooxygenase-2 and inducible nitric oxide synthase in primary hippocampal neuronal culture: Platelet-activating factor as a preferential mediator of cyclooxygenase-2 expression","volume":"58","author":"Serou","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/35068566","article-title":"Interleukin-1\u03b2-mediated induction of COX-2 in the CNS contributes to inflammatory pain hypersensitivity","volume":"410","author":"Samad","year":"2001","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10923","DOI":"10.1523\/JNEUROSCI.19-24-10923.1999","article-title":"An essential role of interleukin-1beta in mediating NF-kappaB activity and COX-2 transcription in cells of the blood-brain barrier in response to a systemic and localized inflammation but not during endotoxemia","volume":"19","author":"Laflamme","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.nbd.2006.10.012","article-title":"Cyclooxygenase-2 mediates the sensitizing effects of systemic IL-1-beta on excitotoxic brain lesions in newborn mice","volume":"25","author":"Favrais","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.mvr.2011.01.006","article-title":"Tumor cells induce COX-2 and mPGES-1 expression in microvascular endothelial cells mainly by means of IL-1 receptor activation","volume":"81","author":"Casos","year":"2011","journal-title":"Microvasc. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1096\/fasebj.10.2.8641570","article-title":"Interleukin-1 receptors on rat brain endothelial cells: A role in neuroimmune interaction?","volume":"10","author":"Kuiper","year":"1996","journal-title":"FASEB J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1523\/JNEUROSCI.3723-13.2014","article-title":"Knockdown of interleukin-1 receptor type-1 on endothelial cells attenuated stress-induced neuroinflammation and prevented anxiety-like behavior","volume":"34","author":"Wohleb","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.bbi.2010.09.009","article-title":"Endothelial IL-1R1 is a critical mediator of EAE pathogenesis","volume":"25","author":"Li","year":"2011","journal-title":"Brain. Behav. Immun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"613","DOI":"10.4049\/jimmunol.0802258","article-title":"Il-1r signaling within the central nervous system regulates CXCL12 expression at the blood-brain barrier and disease severity during experimental autoimmune encephalomyelitis","volume":"183","author":"McCandless","year":"2009","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5811","DOI":"10.4049\/jimmunol.168.11.5811","article-title":"Lipopolysaccharide-dependent prostaglandin E(2) production is regulated by the glutathione-dependent prostaglandin E(2) synthase gene induced by the Toll-like receptor 4\/MYD88\/NF-IL6 pathway","volume":"168","author":"Uematsu","year":"2002","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1093\/brain\/awh260","article-title":"Clinicopathological study of a myelin oligodendrocyte glycoprotein-induced demyelinating disease in LEW.1AV1 rats","volume":"127","author":"Sakuma","year":"2004","journal-title":"Brain"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/j.1750-3639.1998.tb00194.x","article-title":"Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology","volume":"8","author":"Storch","year":"1998","journal-title":"Brain Pathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/11\/3647\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:30:41Z","timestamp":1760196641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/11\/3647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,19]]},"references-count":63,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,11]]}},"alternative-id":["ijms19113647"],"URL":"https:\/\/doi.org\/10.3390\/ijms19113647","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2018,11,19]]}}}