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HIV‐1 Tat Sensitizes Enteric Neurons to Bacterial Proteins
Author(s) -
Ngwainmbi Joy,
Brun Paola,
Kang Minho,
Dewey William,
Hauser Kurt,
Akbarali Hamid
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.628.13
Subject(s) - lipopolysaccharide , cytokine , tumor necrosis factor alpha , enteric nervous system , tlr4 , biology , microbiology and biotechnology , chemistry , immunology , inflammation , endocrinology
HIV infection is characterized by intestinal mucosal damage leading to increased translocation of bacteria and viruses into the gut wall. This exposes enteric neurons to bacterial and viral proteins. Previously, we showed that HIV‐1 Tat, an early HIV protein, increases enteric neuronal excitability and significantly alters gastrointestinal (GI) motility. In this study, we examined cytokine expression by Tat and lipopolysaccharide (LPS) in enteric neurons and its effect on GI transit. Tat sensitized enteric neuron/glia cultures (isolated from adult mouse ileum) to LPS‐induced cytokine release. Neither 10 nM Tat nor 10 ng/ml LPS induced TNF‐ α release, however, they significantly up‐regulated TNF‐ α when treated in combination. This effect was time dependent with the highest sensitization occurring at 6 h Tat treatment. This sensitization effect was also seen in transgenic mice in which LPS (50 µg/kg) treated Tat+ (Tat expressing) mice had robust increases in TNF‐α (7 fold) and IL‐1β (3 fold) mRNA compared to Tat‐ (litter mates) which showed 1.9 and 1.5 fold increases respectively. Tat (100 nM) significantly increased LPS receptor, TLR4, expression by 3 fold. Pellet propulsion was measured using the gastrointestinal motility monitor. Tat+ mice were significantly more sensitive to LPS induced decrease in colonic transit than Tat‐ mice. LPS (50 µg/kg p.o.) reduced colonic transit by 80% in Tat+ mice compared to 35% in Tat‐ mice. These findings suggest that Tat exacerbates the effects of bacterial proteins and enhances opportunistic infections in HIV AIDS. Supported by F31NS087952, DA024009