Activation of Toll-Like Receptor 4 (TLR4) by in Vivo and in Vitro Exposure of Rat Epididymis to Lipopolysaccharide from Escherichia Coli

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dc.contributor.authorRodrigues, Alexandre [UNIFESP]
dc.contributor.authorQueiroz, Daniel B. C. [UNIFESP]
dc.contributor.authorHonda, Luciana [UNIFESP]
dc.contributor.authorSilva, Erick Jose R. [UNIFESP]
dc.contributor.authorHall, Susan H.
dc.contributor.authorAvellar, Maria Christina W. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv N Carolina
dc.date.accessioned2016-01-24T13:51:55Z
dc.date.available2016-01-24T13:51:55Z
dc.date.issued2008-12-01
dc.description.abstractThis study provides the first evidence that rat epididymis is fully capable of initiating an inflammatory response to lipopolysaccharide (LPS) from Escherichia coli through activation of Toll-like receptor 4 (TLR4). TLR4 functionality was demonstrated by in vivo LPS challenge, which induced a time-and dosedependent activation of the transcription factor nuclear factor kappa B (NFKB) in caput and cauda epididymides. NFKB activation by LPS in caput epididymidis was abrogated when rats were pretreated with the NFKB inhibitor PDTC, confirming the specificity of this response. Within 2 h of LPS treatment (0.01 and 1 mg/kg, i.v.), NFKB activation in caput and cauda was accompanied by upregulation of Il1b, Nfkbia, and Cd14, but not Tlr4, mRNA. These effects, however, were not sustained after 24 h of LPS treatment. Lipopolysaccharide systemic effects were not restricted to epididymides, since Il1b, Nfkbia, and Cd14 mRNAs were also upregulated in other male reproductive tissues from LPS-treated rats (1 mg/kg, i.v., 2 h). Constitutive TLR4 was immunolocalized in some, but not all, epididymal epithelial cells and in interstitial cells, some of them identified as resident ED2-positive macrophages. No change in TLR4 immunostaining pattern was observed when epididymides from control and LPS-treated rats were compared (1 mg/kg, i.v., 2 h and 24 h). Significant NFKB activation was also achieved within 1 min of in vitro incubation of caput epididymidis with LPS (0.01-5 mu g/ml), confirming that components for TLR4 signaling cascade activation are fully active in this tissue. This study contributes to a better understanding of the innate immune response in the epididymis and other tissues from the male reproductive tract.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFogarty International Center Program for Training and Research in Population and Health
dc.description.sponsorshipIDFAPESP: 05/55738-8
dc.description.sponsorshipIDCNPq: 475238/2006-0
dc.description.sponsorshipIDFogarty International Center Program for Training and Research in Population and Health: D43TW/HD00627
dc.description.sponsorshipIDFogarty International Center Program for Training and Research in Population and Health: UNIFESP/UNC 5-53284
dc.format.extent1135-1147
dc.identifierhttp://dx.doi.org/10.1095/biolreprod.108.069930
dc.identifier.citationBiology of Reproduction. Madison: Soc Study Reproduction, v. 79, n. 6, p. 1135-1147, 2008.
dc.identifier.doi10.1095/biolreprod.108.069930
dc.identifier.issn0006-3363
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/31054
dc.identifier.wosWOS:000261167600015
dc.language.isoeng
dc.publisherSoc Study Reproduction
dc.relation.ispartofBiology of Reproduction
dc.rightsAcesso aberto
dc.subjectepididymisen
dc.subjectgene regulationen
dc.subjectlipopolysaccharideen
dc.subjectrodenten
dc.subjecttranscription factoren
dc.titleActivation of Toll-Like Receptor 4 (TLR4) by in Vivo and in Vitro Exposure of Rat Epididymis to Lipopolysaccharide from Escherichia Colien
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