Sulfur Compounds Inhibit High Glucose-Induced Inflammation by Regulating NF-κB Signaling in Human Monocytes.

Eun Seong Jo,Dong Young Kang,Young Mok Yang,Il Ho Kim,Nipin Sp,Se Won Bae,Kyoung-Jin Jang,Alexis Rugamba,Qing Liu

doi:10.3390/molecules25102342

Abstract

High glucose-induced inflammation leads to atherosclerosis, which is considered a major cause of death in type 1 and type 2 diabetic patients. Nuclear factor-kappa B (NF-κB) plays a central role in high glucose-induced inflammation and is activated through toll-like receptors (TLRs) as well as canonical and protein kinase C-dependent (PKC) pathways. Non-toxic sulfur (NTS) and methylsulfonylmethane (MSM) are two sulfur-containing natural compounds that can induce anti-inflammation. Using Western blotting, real-time polymerase chain reaction, and flow cytometry, we found that high glucose-induced inflammation occurs through activation of TLRs. An effect of NTS and MSM on canonical and PKC-dependent NF-κB pathways was also demonstrated by western blotting. The effects of proinflammatory cytokines were investigated using a chromatin immunoprecipitation assay and enzyme-linked immunosorbent assay. Our results showed inhibition of the glucose-induced expression of TLR2 and TLR4 by NTS and MSM. These sulfur compounds also inhibited NF-κB activity through reactive oxygen species (ROS)-mediated canonical and PKC-dependent pathways. Finally, NTS and MSM inhibited the high glucose-induced expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and binding of NF-κB protein to the DNA of proinflammatory cytokines. Together, these results suggest that NTS and MSM may be potential drug candidates for anti-inflammation therapy.

Highlights

Atherosclerosis is a disease caused by the deposition of plaques of fatty substances on the inner walls of arteries and is considered the main factor contributing to death in type 1 and type 2 diabetes [1,2]
We identified glucose that inducedthe inflammatory effects, andofwe found that the THP-1 glucose concentration of 202 mM
We identified the highest concentration of glucose increased the expression of NF-κB, TLR4, p-IκBα, p-IKKα/β, and p-ERK in THP-1 cells (Figure S1)

Summary

Introduction

Atherosclerosis is a disease caused by the deposition of plaques of fatty substances on the inner walls of arteries and is considered the main factor contributing to death in type 1 and type 2 diabetes [1,2]. Glucose is the key factor that induces these conditions, in which high glucose may lead to the accumulation of diacylglycerol and the activation of protein kinase C (PKC) in vascular cells, thereby. High glucose conditions activate NF-κB, which activates various inflammatory genes, including adhesion molecules that promote the adhesion of monocytes to endothelial cells [3]. As a result of inflammation, pathogen-associated molecular patterns and inflammatory cytokines stimulate certain cell surface receptors, such as toll-like receptors (TLRs), to activate NF-κB and initiate inflammatory immune response signaling pathways [7]. TLRs identify molecular patterns in response to pathogens to induce innate immune responses [8,9]. The activation of TLRs triggers the signaling pathway to produce cytokines and initiate an immune response [10]

Methods

Results

Discussion

Conclusion