Depurinized milk downregulates rat thymus MyD88/Akt/p38 function, NF-\u03baB-mediated inflammation, caspase-1 activity but not the endonuclease pathway: in vitro/in vivo study

Gordana Kocic,Hristina Kocic,Andrej Veljkovic,Katarina Tomovic,Dusan Mihajlovic,Miodrag Colic,Svetlana Stojanovic,Miodrag Colic,Andrija Smelcerovic

doi:10.1038/srep41971

Gordana Kocic, Hristina Kocic + Show 7 more

Open Access

https://doi.org/10.1038/srep41971

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Abstract

The aim of this study was the evaluation of 15 days dietary regimen of depurinized (DP) milk (obtained using our patented technological procedures) or 1.5% fat UHT milk instead of standard chow diet, on rat thymus and bone marrow MyD88/Akt/p38, NF-κB, caspase-1 and endonuclease pathways, in relation to peripheral blood cell composition. To determine whether the reduced mass of the thymus is a consequence of the direct effect of DP/UHT milk on apoptosis of thymocytes, in vitro Annexin-V-FITC/PI assay was performed. Significant decreases in the thymus wet weight, thymocyte MyD88, Akt-1/phospho-Akt-1 kinase, p38/phospho-p38, NF-κB, caspase-1 activity and CD4+/CD8+ antigen expression were obtained, especially in the DP milk group. The activity of thymocyte alkaline and acid DNase increased in the DP but not in the UHT milk group. The level of IL-6 significantly decreased in DP milk treated group, while the level of total TGF-β and IL-6 increased in UHT milk group. Significant differences in hematological parameters were obtained in commercial milk fed group. Observed results about prevention of experimental diabetes in DP pretreated groups may suggest that purine compounds, uric acid and other volatile toxic compounds of commercial milk may suppress oral tolerance, probably via IL-6 and TGF-β cytokine effects.

Highlights

In recent years, the personalized nutrition concept has suggested that cow milk is a powerful epigenetic modulator of cell signaling, predominantly based on its endocrine components, essential amino acids, nucleotides and bioactive bovine exosomal microRNAs
DP milk and UHT milk led to significant decreases in thymocyte MyD88, Akt-1 kinase/phospho-Akt-1 kinase, p38/phospho-p38, NF-κB, CD4+and CD8+antigen expression; the CD4+lineage was more affected than the CD8+; and the effect was more pronounced for the DP milk group (Figs 1 and 2)
Our experimental study showed that compared to dietary milk regimens with commercial UHT cow milk, the newly patented DP milk diet led to significant thymus atrophy after feeding rats for 15 days, which was absolute and relative

Summary

Introduction

The personalized nutrition concept has suggested that cow milk is a powerful epigenetic modulator of cell signaling, predominantly based on its endocrine components (insulin-like growth factor 1, IGF-1), essential amino acids, nucleotides and bioactive bovine exosomal microRNAs. It was documented that epigenetic cell signaling may have downstream targets, such as the nutrient-sensitive kinase rapamycin complex (mammalian target of rapamycin complex 1, mTORC1), which, upon phosphorylation, can exert an influence on the functional activity of cell transcription factors, DNA fragmentation and posttranscriptional RNA modification. It was documented that epigenetic cell signaling may have downstream targets, such as the nutrient-sensitive kinase rapamycin complex (mammalian target of rapamycin complex 1, mTORC1), which, upon phosphorylation, can exert an influence on the functional activity of cell transcription factors, DNA fragmentation and posttranscriptional RNA modification This may modulate proliferation and intermediary metabolism, while in the thymic medulla, some exosome carriers may act as signals for immune communication[1,2,3]. In addition to its apoptotic influence, caspase-1 may trigger inflammatory and autoimmune reactions[31,32,33]

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