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Analyzing Beneficial Effects of Nutritional Supplements on Intestinal Epithelial Barrier Functions During Experimental Colitis
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Matrix Metalloproteinase-9 Signaling Regulates Colon Barrier Integrity in Models of HIV Infection.

Michael Ohene-Nyako1,2,3, Amanda L Persons4,2, Christopher Forsyth5,6,7

  • 1Department of Pharmacology, Rush University Medical Center, 1735 W. Harrison Street Cohn Research Building Suite #424, Chicago, IL, 60612, USA.

Journal of Neuroimmune Pharmacology : the Official Journal of the Society on Neuroimmune Pharmacology
|November 5, 2024
PubMed
Summary

Human immunodeficiency virus (HIV) proteins damage the gut barrier by decreasing occludin and increasing MMP-9. Pioglitazone, a PPARγ agonist, protected against these HIV-induced gut barrier disruptions.

Keywords:
Caco-2 cellsERKHIV-1 transgenic ratNFκBPPARγ

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Area of Science:

  • Gastroenterology
  • Virology
  • Immunology

Background:

  • HIV infection compromises gut barrier integrity, leading to systemic inflammation.
  • HIV-1 transgenic rats exhibit disrupted colon epithelial barrier proteins.
  • Methamphetamine use is common in HIV-infected individuals and may worsen health outcomes.

Purpose of the Study:

  • To investigate mechanisms of HIV-associated gut barrier pathology.
  • To determine if methamphetamine exacerbates HIV-related gut issues.
  • To evaluate the role of HIV-1 toxic proteins and potential therapeutic interventions.

Main Methods:

  • Analysis of colon samples from HIV-1 transgenic and non-transgenic rats exposed to methamphetamine.
  • Immunoblotting for occludin and matrix metalloproteinase-9 (MMP-9).
  • In vitro studies using Caco-2 cells exposed to HIV-1 Tat protein and pioglitazone.

Main Results:

  • HIV-1 transgenic rats showed decreased occludin and increased MMP-9 levels and activity.
  • A significant inverse correlation was found between occludin levels and MMP-9 activity.
  • HIV-1 Tat protein decreased transepithelial resistance and tight junction proteins in Caco-2 cells, an effect mitigated by pioglitazone.

Conclusions:

  • HIV-1 proteins disrupt the gut barrier through MMP-9 dysregulation.
  • Low-dose methamphetamine did not significantly worsen HIV-associated gut pathology in this model.
  • Pioglitazone demonstrates potential in preventing and restoring HIV-induced gut barrier damage.