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High glucose induces a priming effect in macrophages and exacerbates the production of pro-inflammatory cytokines after a challenge

Authors Grosick R, Alvarado-Vazquez PA, Messersmith AR, Romero-Sandoval EA

Received 3 February 2018

Accepted for publication 14 May 2018

Published 7 September 2018 Volume 2018:11 Pages 1769—1778

DOI https://doi.org/10.2147/JPR.S164493

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Erica Wegrzyn


Rachel Grosick,1 Perla Abigail Alvarado-Vazquez,2 Amy R Messersmith,1 E Alfonso Romero-Sandoval2

1Department of Pharmaceutical and Administrative Science, Presbyterian College School of Pharmacy, Clinton, SC, USA; 2Department of Anesthesiology, Wake Forest University School Medicine, Winston-Salem, NC, USA

Introduction: Painful diabetic neuropathy is associated with chronic inflammation, in which macrophages are the key effectors. We utilized an in vitro approach to determine the effects of high glucose on macrophage phenotype.
Materials and methods: We exposed human THP-1 macrophages to normal glucose (5 mM) and a clinically relevant high glucose environment (15 mM) and measured the expression and concentration of molecules associated with a diabetic cellular phenotype.
Results: We found that THP-1 macrophages in high glucose conditions did not influence the basal expression of cyclooxygenase-2, Toll-like receptor-4, or class A scavenger receptor mRNA, or the concentrations of the cytokines interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and IL-10, but induced a priming effect on tumor necrosis factor (TNF)-α. Then, we stimulated THP-1 macrophages with a strong pro-inflammatory stimulus lipopolysaccharide (LPS; 5 µg/mL). After stimulation with LPS, we observed an exacerbated increase in TNF-α, IL-6, and MCP-1 concentration in the high glucose condition compared to the normal glucose environment. THP-1 macrophages in high glucose conditions developed tolerance to IL-10 anti-inflammatory effects (TNF-α production) when challenged with LPS.
Conclusion: Our in vitro approach allows the study of macrophages as potential targets for therapeutic purposes since it compares them to primary human macrophages exposed to high glucose and macrophages from patients with diabetes or complications of painful diabetic neuropathy (i.e. ulcers, adipocytes, and pancreas).

Keywords: diabetes, hyperglycemia, THP-1, monocyte, TNF, inflammation

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