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HIV-1 Tat-induced diarrhea is improved by the PPARalpha agonist, palmitoylethanolamide, by suppressing the activation of enteric glia.
Sarnelli, Giovanni; Seguella, Luisa; Pesce, Marcella; Lu, Jie; Gigli, Stefano; Bruzzese, Eugenia; Lattanzi, Roberta; D'Alessandro, Alessandra; Cuomo, Rosario; Steardo, Luca; Esposito, Giuseppe.
Afiliação
  • Sarnelli G; Department of Clinical Medicine and Surgery, "Federico II" University of Naples, 80131, Naples, Italy. sarnelli@unina.it.
  • Seguella L; Department of Physiology and Pharmacology, "Vittorio Erspamer", La Sapienza University of Rome, 00185, Rome, Italy.
  • Pesce M; Department of Clinical Medicine and Surgery, "Federico II" University of Naples, 80131, Naples, Italy.
  • Lu J; Department of Anatomy, China Medical University, Shenyang, Liaoning Province, 110122, People's Republic of China.
  • Gigli S; Department of Physiology and Pharmacology, "Vittorio Erspamer", La Sapienza University of Rome, 00185, Rome, Italy.
  • Bruzzese E; Department of Translational Medical Science, Section of Pediatrics, University Federico II, 80131, Naples, Italy.
  • Lattanzi R; Department of Physiology and Pharmacology, "Vittorio Erspamer", La Sapienza University of Rome, 00185, Rome, Italy.
  • D'Alessandro A; Department of Clinical Medicine and Surgery, "Federico II" University of Naples, 80131, Naples, Italy.
  • Cuomo R; Department of Clinical Medicine and Surgery, "Federico II" University of Naples, 80131, Naples, Italy.
  • Steardo L; Department of Clinical Medicine and Surgery, "Federico II" University of Naples, 80131, Naples, Italy.
  • Esposito G; Department of Physiology and Pharmacology, "Vittorio Erspamer", La Sapienza University of Rome, 00185, Rome, Italy.
J Neuroinflammation ; 15(1): 94, 2018 Mar 24.
Article em En | MEDLINE | ID: mdl-29573741
BACKGROUND: Diarrhea is a severe complication in HIV-1-infected patients with Trans-activator of transcription (HIV-1 Tat) protein being recognized as a major underlying cause. Beside its direct enterotoxic effects, Tat protein has been recently shown to affect enteric glial cell (EGC) activity. EGCs regulate intestinal inflammatory responses by secreting pro-inflammatory molecules; nonetheless, they might also release immune-regulatory factors, as palmytoilethanolamide (PEA), which exerts anti-inflammatory effects by activating PPARα receptors. We aimed at clarifying whether EGCs are involved in HIV-1 Tat-induced diarrhea and if PEA exerts antidiarrheal activity. METHODS: Diarrhea was induced by intracolonic administration of HIV-1 Tat protein in rats at day 1. PEA alone or in the presence of peroxisome proliferator-activated receptor (PPAR) antagonists was given intraperitoneally from day 2 to day 7. S100B, iNOS, NF-kappaB, TLR4 and GFAP expression were evaluated in submucosal plexi, while S100B and NO levels were measured in EGC submucosal plexi lysates, respectively. To verify whether PEA effects were PPARα-mediated, PPARα-/- mice were also used. After 7 days from diarrhea induction, endogenous PEA levels were measured in submucosal plexi homogenates deriving from rats and PPARα-/- mice. RESULTS: HIV-1 Tat protein induced rapid onset diarrhea alongside with a significant activation of EGCs. Tat administration significantly increased all hallmarks of neuroinflammation by triggering TLR4 and NF-kappaB activation and S100B and iNOS expression. Endogenous PEA levels were increased following HIV-1 Tat exposure in both wildtype and knockout animals. In PPARα-/- mice, PEA displayed no effects. In wildtype rats, PEA, via PPARα-dependent mechanism, resulted in a significant antidiarrheal activity in parallel with marked reduction of EGC-sustained neuroinflammation. CONCLUSIONS: EGCs mediate HIV-1 Tat-induced diarrhea by sustaining the intestinal neuroinflammatory response. These effects are regulated by PEA through a selective PPARα-dependent mechanism. PEA might be considered as an adjuvant therapy in HIV-1-induced diarrhea.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Ácidos Palmíticos / Neuroglia / Diarreia / Etanolaminas / Produtos do Gene tat do Vírus da Imunodeficiência Humana Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Neuroinflammation Assunto da revista: NEUROLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Ácidos Palmíticos / Neuroglia / Diarreia / Etanolaminas / Produtos do Gene tat do Vírus da Imunodeficiência Humana Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Neuroinflammation Assunto da revista: NEUROLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Itália