Your browser doesn't support javascript.
loading
HIV-1 Tat exacerbates lipopolysaccharide-induced cytokine release via TLR4 signaling in the enteric nervous system.
Guedia, Joy; Brun, Paola; Bhave, Sukhada; Fitting, Sylvia; Kang, Minho; Dewey, William L; Hauser, Kurt F; Akbarali, Hamid I.
Afiliação
  • Guedia J; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • Brun P; Department of Molecular Medicine, University of Padova, Padova, Italy.
  • Bhave S; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • Fitting S; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • Kang M; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • Dewey WL; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • Hauser KF; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • Akbarali HI; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Sci Rep ; 6: 31203, 2016 08 05.
Article em En | MEDLINE | ID: mdl-27491828
ABSTRACT
The loss of gut epithelium integrity leads to translocation of microbes and microbial products resulting in immune activation and drives systemic inflammation in acquired immunodeficiency syndrome (AIDS) patients. Although viral loads in HIV patients are significantly reduced in the post-cART era, inflammation and immune activation persist and can lead to morbidity. Here, we determined the interactive effects of the viral protein HIV-1 Tat and lipopolysaccharide (LPS) on enteric neurons and glia. Bacterial translocation was significantly enhanced in Tat-expressing (Tat+) mice. Exposure to HIV-1 Tat in combination with LPS enhanced the expression and release of the pro-inflammatory cytokines IL-6, IL-1ß and TNF-α in the ilea of Tat+ mice and by enteric glia. This coincided with enhanced NF-κB activation in enteric glia that was abrogated in glia from TLR4 knockout mice and by knockdown (siRNA) of MyD88 siRNA in wild type glia. The synergistic effects of Tat and LPS resulted in a reduced rate of colonic propulsion in Tat+ mice treated with LPS. These results show that HIV-1 Tat interacts with the TLR4 receptor to enhance the pro-inflammatory effects of LPS leading to gastrointestinal dysmotility and enhanced immune activation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por HIV / Citocinas / HIV-1 / Sistema Nervoso Entérico / Translocação Bacteriana / Receptor 4 Toll-Like / Produtos do Gene tat do Vírus da Imunodeficiência Humana Limite: Animals / Humans Idioma: En Revista: Sci Rep Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por HIV / Citocinas / HIV-1 / Sistema Nervoso Entérico / Translocação Bacteriana / Receptor 4 Toll-Like / Produtos do Gene tat do Vírus da Imunodeficiência Humana Limite: Animals / Humans Idioma: En Revista: Sci Rep Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos