期刊
MOLECULES
卷 25, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/molecules25102342
关键词
High glucose; Diabetes; TLRs; NF-kappa B; Canonical pathway; PKC pathway; Proinflammatory cytokines
资金
- Nara Bio Co., Ltd., Republic of Korea
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2017R1A6A3A01010180, 2018R1D1A1B07048651]
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [2018R1C1B6006146]
- National Research Foundation of Korea [2017R1A6A3A01010180, 2018R1D1A1B07048651, 2018R1C1B6006146] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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-kappa B) 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-kappa B 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-kappa B 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)-1 beta, IL-6, and tumor necrosis factor-alpha and binding of NF-kappa B protein to the DNA of proinflammatory cytokines. Together, these results suggest that NTS and MSM may be potential drug candidates for anti-inflammation therapy.
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