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

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

Autor Rodrigues, Alexandre Autor UNIFESP Google Scholar
Queiroz, Daniel B. C. Autor UNIFESP Google Scholar
Honda, Luciana Autor UNIFESP Google Scholar
Silva, Erick Jose R. Autor UNIFESP Google Scholar
Hall, Susan H. Google Scholar
Avellar, Maria Christina W. Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Univ N Carolina
Resumo This 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.
Palavra-chave epididymis
gene regulation
lipopolysaccharide
rodent
transcription factor
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fogarty International Center Program for Training and Research in Population and Health
Número do financiamento FAPESP: 05/55738-8
CNPq: 475238/2006-0
Fogarty International Center Program for Training and Research in Population and Health: D43TW/HD00627
Fogarty International Center Program for Training and Research in Population and Health: UNIFESP/UNC 5-53284
Data de publicação 2008-12-01
Publicado em Biology of Reproduction. Madison: Soc Study Reproduction, v. 79, n. 6, p. 1135-1147, 2008.
ISSN 0006-3363 (Sherpa/Romeo, fator de impacto)
Publicador Soc Study Reproduction
Extensão 1135-1147
Fonte http://dx.doi.org/10.1095/biolreprod.108.069930
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000261167600015
Endereço permanente http://repositorio.unifesp.br/handle/11600/31054

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