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.