Vitamin D Status Modulates Inflammatory Response in HIV+ Subjects: Evidence for Involvement of Autophagy and TG2 Expression in PBMC

Int J Mol Sci. 2020 Oct 13;21(20):7558. doi: 10.3390/ijms21207558.

Abstract

Conflicting results on the involvement of vitamin D deficiency in inflammatory and immune response in HIV+ subjects are reported. We aimed to characterize the possible influence of vitamin D status on changes in expression of tissue transglutaminase gene (TGM2) and other genes involved in inflammatory response and autophagy in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. HIV+ subjects (n = 57) under antiretroviral therapy (ART) and healthy controls (n = 40) were enrolled. mRNA levels of 1-alpha-hydroxylase (CYP27B1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), TGM2, microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related 5 homolog (ATG5), and Beclin 1 (BECN1) were quantified by real-time PCR. In HIV+ subjects, 25(OH)D3 plasma levels were negatively correlated with time since HIV diagnosis. In PBMC from HIV+ subjects, increases in gene expression of TNF-α and IFN-γ in comparison to controls were observed. The highest increase in TNF-α transcripts was observed in HIV+ subjects with deficient 25(OH)D3 levels. Autophagy-related genes LC3, ATG5, and BECN1 were down-regulated in HIV+ subjects. Moreover, TGM2 transcripts were up-regulated in PBMC from HIV+ subjects with 25(OH)D3 deficiency. Changes observed in PBMC from HIV+ subjects appeared to be dependent on vitamin D status. The present results suggest that vitamin D deficiency is associated with changes in the expression of markers of inflammation and autophagy, resulting in immune cell dysfunction.

Keywords: HIV; autophagy; cytokines; inflammation; peripheral blood mononuclear cells; tissue transglutaminase; vitamin D.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Adult
  • Autophagy*
  • Autophagy-Related Protein 5 / genetics
  • Autophagy-Related Protein 5 / metabolism
  • Beclin-1 / genetics
  • Beclin-1 / metabolism
  • Female
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • HIV Infections / blood
  • HIV Infections / metabolism*
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Male
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Monocytes / metabolism*
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases / genetics*
  • Transglutaminases / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Vitamin D / blood*

Substances

  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • BECN1 protein, human
  • Beclin-1
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • TGM2 protein, human
  • Tumor Necrosis Factor-alpha
  • Vitamin D
  • Interferon-gamma
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • CYP27B1 protein, human
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins