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

International Journal of Molecular Sciences

Monica Currò¹  Nadia Ferlazzo¹  Riccardo Ientile¹  MariaGiovanna Costanzo¹  Daniela Caccamo¹  Giuseppa Visalli¹  Giuseppe Nunnari²  Flavia D’Andrea²  GiovanniFrancesco Pellicanò³ 

[1] Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy;Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy;Unit of Infectious Diseases, Department of Human Pathology of Adult and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, Italy;

关键词: autophagy;    cytokines;    HIV;    inflammation;    peripheral blood mononuclear cells;    tissue transglutaminase;   

DOI  :  10.3390/ijms21207558

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown