{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360565166014632064.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1016/j.lfs.2012.06.030"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0024320512003384?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0024320512003384?httpAccept=text/plain"}},{"identifier":{"@type":"PMID","@value":"22771700"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Trypsin inhibits lipopolysaccharide signaling in macrophages via toll-like receptor 4 accessory molecules"}],"description":[{"notation":[{"@value":"To examine the role of trypsin in the immune response of macrophages and to determine whether protease-activated receptors (PARs) are involved in the effects of trypsin.We used RAW264.7 cells and peritoneal macrophages isolated from C57BL/6 wild-type mice, PAR2 knockout mice, and ddY mice. Macrophages were stimulated with lipopolysaccharide (LPS) in the presence or absence of trypsin, thrombin, and PAR subtype-specific agonists (PARs-AP). Activation of macrophages was quantified by nitric oxide production and expression of inflammatory mediators, such as inducible nitric oxide synthase, interleukin-1β, and interleukin-6. To clarify the effect of trypsin on LPS receptors, we also investigated the expression of toll-like receptor 4 (TLR4), soluble MD-2 (sMD-2), membrane-bound MD-2 (mMD-2), soluble CD14 (sCD14), and membrane-bound CD14 (mCD14). To directly investigate the effect of trypsin on CD14 protein, we expressed recombinant CD14 protein.Trypsin inhibited LPS-induced nitric oxide production and expression of inducible nitric oxide synthase, interleukin-1β, and interleukin-6. The same inhibitory effects of trypsin were observed in wild-type macrophages and in PAR2 knockout macrophages. Furthermore, the other PAR agonists, thrombin, PAR1-AP, PAR2-AP, and PAR4-AP, did not mimic the effect of trypsin. Although trypsin did not affect TLR4 or mMD-2 expression, sCD14, mCD14, and sMD-2 expressions were decreased by trypsin. Furthermore, trypsin also degraded recombinant CD14 protein.Trypsin inhibited LPS signaling PAR-independently via degradation of TLR4 accessory molecules. This observation provides a better understanding of the complicated immune response in acute pancreatitis."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380284919212031744","@type":"Researcher","foaf:name":[{"@value":"Hiroyuki Komatsu"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919212031749","@type":"Researcher","foaf:name":[{"@value":"Akihiro Shimose"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919212031745","@type":"Researcher","foaf:name":[{"@value":"Takashi Shimizu"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919212031747","@type":"Researcher","foaf:name":[{"@value":"Yu Mukai"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919212031748","@type":"Researcher","foaf:name":[{"@value":"Jun Kobayashi"}]},{"@id":"https://cir.nii.ac.jp/crid/1420845751140929536","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"50579018"},{"@type":"NRID","@value":"1000050579018"},{"@type":"NRID","@value":"9000345269549"},{"@type":"NRID","@value":"9000006427853"},{"@type":"NRID","@value":"9000411384476"},{"@type":"NRID","@value":"9000022076948"},{"@type":"NRID","@value":"9000265246598"},{"@type":"NRID","@value":"9000391399695"},{"@type":"NRID","@value":"9000329440526"},{"@type":"NRID","@value":"9000021953024"},{"@type":"NRID","@value":"9000293528376"},{"@type":"NRID","@value":"9000021953007"},{"@type":"NRID","@value":"9000386309267"},{"@type":"NRID","@value":"9000257759482"},{"@type":"NRID","@value":"9000018574265"},{"@type":"NRID","@value":"9000356685606"},{"@type":"NRID","@value":"9000345267042"},{"@type":"NRID","@value":"9000240042178"},{"@type":"NRID","@value":"9000404666405"},{"@type":"NRID","@value":"9000020620732"},{"@type":"NRID","@value":"9000022059493"},{"@type":"NRID","@value":"9000414259800"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/7000022132"}],"foaf:name":[{"@value":"Takashi Ohama"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326225710848","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"90205914"},{"@type":"NRID","@value":"1000090205914"},{"@type":"NRID","@value":"9000259330535"},{"@type":"NRID","@value":"9000345269550"},{"@type":"NRID","@value":"9000397814452"},{"@type":"NRID","@value":"9000002065608"},{"@type":"NRID","@value":"9000025042066"},{"@type":"NRID","@value":"9000411384477"},{"@type":"NRID","@value":"9000405365241"},{"@type":"NRID","@value":"9000265246599"},{"@type":"NRID","@value":"9000021953025"},{"@type":"NRID","@value":"9000021953006"},{"@type":"NRID","@value":"9000257759483"},{"@type":"NRID","@value":"9000020941698"},{"@type":"NRID","@value":"9000311503909"},{"@type":"NRID","@value":"9000240042179"},{"@type":"NRID","@value":"9000404666407"},{"@type":"NRID","@value":"9000020620735"},{"@type":"NRID","@value":"9000022059495"},{"@type":"NRID","@value":"9000414259801"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0207071"}],"foaf:name":[{"@value":"Koichi Sato"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00243205"}],"prism:publicationName":[{"@value":"Life Sciences"}],"dc:publisher":[{"@value":"Elsevier BV"}],"prism:publicationDate":"2012-08","prism:volume":"91","prism:number":"3-4","prism:startingPage":"143","prism:endingPage":"150"},"reviewed":"false","dc:rights":["https://www.elsevier.com/tdm/userlicense/1.0/","https://www.elsevier.com/legal/tdmrep-license"],"url":[{"@id":"https://api.elsevier.com/content/article/PII:S0024320512003384?httpAccept=text/xml"},{"@id":"https://api.elsevier.com/content/article/PII:S0024320512003384?httpAccept=text/plain"}],"createdAt":"2012-07-05","modifiedAt":"2025-09-20","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Inflammation","dc:title":"Inflammation"},{"@id":"https://cir.nii.ac.jp/all?q=Lipopolysaccharides","dc:title":"Lipopolysaccharides"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Knockout","dc:title":"Mice, Knockout"},{"@id":"https://cir.nii.ac.jp/all?q=Macrophages","dc:title":"Macrophages"},{"@id":"https://cir.nii.ac.jp/all?q=Receptors,%20Proteinase-Activated","dc:title":"Receptors, Proteinase-Activated"},{"@id":"https://cir.nii.ac.jp/all?q=Lipopolysaccharide%20Receptors","dc:title":"Lipopolysaccharide Receptors"},{"@id":"https://cir.nii.ac.jp/all?q=Thrombin","dc:title":"Thrombin"},{"@id":"https://cir.nii.ac.jp/all?q=Nitric%20Oxide","dc:title":"Nitric Oxide"},{"@id":"https://cir.nii.ac.jp/all?q=Real-Time%20Polymerase%20Chain%20Reaction","dc:title":"Real-Time Polymerase Chain Reaction"},{"@id":"https://cir.nii.ac.jp/all?q=Recombinant%20Proteins","dc:title":"Recombinant Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20C57BL","dc:title":"Mice, Inbred C57BL"},{"@id":"https://cir.nii.ac.jp/all?q=Toll-Like%20Receptor%204","dc:title":"Toll-Like Receptor 4"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Trypsin","dc:title":"Trypsin"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000782029073792","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"20228005"},{"@type":"JGN","@value":"JP20228005"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20228005/"}],"notation":[{"@language":"ja","@value":"間葉系細胞の免疫応答に着目した腸肝軸多段階免疫バリアーシステムの研究"},{"@language":"en","@value":"Studies on the phased immune-barrier systems in gut-liver axis  focusing on immune responses of mesenchymal 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