ArticleJournal of neuroinflammation2018
HIV-1 Tat-induced diarrhea is improved by the PPARalpha agonist, palmitoylethanolamide, by suppressing the activation of enteric glia.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Global research status and trends of enteric glia: a bibliometric analysis.Frontiers in pharmacology · 2024Pooled it
- The Prospects of Palmitylethanolamide in Tumor Prevention and Treatment.Journal of inflammation research · 2026Review
- The Physiology of Enteric Glia.Annual review of physiology · 2025Review
- WKB ameliorates DSS-induced colitis through inhibiting enteric glial cells activation and altering the intestinal microbiota.Journal of translational medicine · 2025Article
- HIV and the gut: implications for HIV persistence, immune dysfunction and cure strategies.Frontiers in immunology · 2025Review
- Mini-review: Enteric glial cell reactions to inflammation and potential therapeutic implications for GI diseases, motility disorders, and abdominal pain.Neuroscience letters · 2023Article
- Harnessing the Power of Enteric Glial Cells' Plasticity and Multipotency for Advancing Regenerative Medicine.International journal of molecular sciences · 2023Review
- Enteric nervous system as a target and source of SARS-CoV-2 and other viral infections.American journal of physiology. Gastrointestinal and liver physiology · 2023Review
- HIV Tat Expression and Cocaine Exposure Lead to Sex- and Age-Specific Changes of the Microbiota Composition in the Gut.Microorganisms · 2023Article
- Enteric glia as a player of gut-brain interactions during Parkinson's disease.Frontiers in neuroscience · 2023Review
- The Enteric Glia and Its Modulation by the Endocannabinoid System, a New Target for Cannabinoid-Based Nutraceuticals?Molecules (Basel, Switzerland) · 2022Review
- Palmitoylethanolamide and Related ALIAmides for Small Animal Health: State of the Art.Biomolecules · 2022Review
- N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism.Biomolecules · 2022Article
- The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study.Medical sciences (Basel, Switzerland) · 2022Article
- New insights into pathogenesis point to HIV-1 Tat as a key vaccine target.Archives of virology · 2021Review
- Enteric glial biology, intercellular signalling and roles in gastrointestinal disease.Nature reviews. Gastroenterology & hepatology · 2021Review
- Nutraceuticals and Enteric Glial Cells.Molecules (Basel, Switzerland) · 2021Review
- You Talking to Me? Says the Enteric Nervous System (ENS) to the Microbe. How Intestinal Microbes Interact with the ENS.Journal of clinical medicine · 2020Review
- Palmitoylethanolamide and Related ALIAmides: Prohomeostatic Lipid Compounds for Animal Health and Wellbeing.Veterinary sciences · 2020Review
- PPARα-targeted mitochondrial bioenergetics mediate repair of intestinal barriers at the host-microbe intersection during SIV infection.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiarrhea 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.
methodsDiarrhea 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
resultsHIV-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
conclusionsEGCs 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.