TLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathway

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dc.contributor.authorCruz-Machado, Sanseray da Silveira
dc.contributor.authorCarvalho-Sousa, Claudia Emanuele
dc.contributor.authorTamura, Eduardo Koji
dc.contributor.authorPinato, Luciana
dc.contributor.authorCecon, Erika
dc.contributor.authorMagno Fernandes, Pedro Augusto Carlos
dc.contributor.authorAvellar, Maria Christina Werneck [UNIFESP]
dc.contributor.authorFerreira, Zulma Silva
dc.contributor.authorMarkus, Regina Pekelmann
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniv Estadual Paulista
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:05:27Z
dc.date.available2016-01-24T14:05:27Z
dc.date.issued2010-09-01
dc.description.abstractNuclear factor-kappa B (NFKB), a pivotal player in inflammatory responses, is constitutively expressed in the pineal gland. Corticosterone inhibits pineal NFKB leading to an enhancement of melatonin production, while tumor necrosis factor (TNF) leads to inhibition of Aa-nat transcription and the production of N-acetylserotonin in cultured glands. the reduction in nocturnal melatonin surge favors the mounting of the inflammatory response. Despite these data, there is no clear evidence of the ability of the pineal gland to recognize molecules that signal infection. This study investigated whether the rat pineal gland expresses receptors for lipopolysaccharide (LPS), the endotoxin from the membranes of Gram-negative bacteria, and to establish the mechanism of action of LPS. Here, we show that pineal glands possess both CD14 and toll-like receptor 4 (TLR4), membrane proteins that bind LPS and trigger the NFKB pathway. LPS induced the nuclear translocation of p50/p50 and p50/RELA dimers and the synthesis of TNF. the maximal expression of TNF in cultured glands coincides with an increase in the expression of TNF receptor 1 (TNFR1) in isolated pinealocytes. in addition, LPS inhibited the synthesis of N-acetylserotonin and melatonin. Therefore, the pineal gland transduces Gram-negative endotoxin stimulation by producing TNF and inhibiting melatonin synthesis. Here, we provide evidence to reinforce the idea of an immune-pineal axis, showing that the pineal gland is a constitutive player in the innate immune response.en
dc.description.affiliationUniv São Paulo, Lab Cronofarmacol, Inst Biociencias, BR-05508900 São Paulo, Brazil
dc.description.affiliationUniv Estadual Paulista, Dept Speech Language & Hearing Therapy, Marilia, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.description.sponsorshipIDFAPESP: 2006/57009-6pt
dc.description.sponsorshipIDFAPESP: 2007/07871-6pt
dc.description.sponsorshipIDCNPq: 484206-2006-0pt
dc.format.extent183-192
dc.identifierhttps://dx.doi.org/10.1111/j.1600-079X.2010.00785.x
dc.identifier.citationJournal of Pineal Research. Hoboken: Wiley-Blackwell, v. 49, n. 2, p. 183-192, 2010.
dc.identifier.doi10.1111/j.1600-079X.2010.00785.x
dc.identifier.issn0742-3098
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/32893
dc.identifier.wosWOS:000280645700011
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofJournal of Pineal Research
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectLipopolysaccharideen
dc.subjectMelatoninen
dc.subjectNuclear factor-kappa Ben
dc.subjectPineal glanden
dc.subjectToll-like receptor 4en
dc.subjectTumor necrosis factoren
dc.titleTLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathwayen
dc.typeinfo:eu-repo/semantics/article
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