Methylsulfonylmethane (MSM), also known as dimethyl sulfone and methyl sulfone, 
is an organic sulfur-containing compound that occurs naturally in a variety of 
fruits, vegetables, grains, and animals, including humans. In the present study, 
we demonstrated the anti-inflammatory effects of MSM in lipopolysaccharide 
(LPS)-stimulated murine macrophages, RAW264.7 cells. MSM significantly inhibited 
the release of nitric oxide and prostaglandin E(2) by alleviating the expression 
of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-stimulated 
RAW264.7 cells. Furthermore, the levels of interleukin-6 and tumor necrosis 
factor-alpha were decreased by MSM treatment in cell culture supernatants. 
Further study indicated that the translocation of the p65 subunit of nuclear 
factor (NF)-kappaB to the nucleus was inhibited by MSM treatment in 
LPS-stimulated RAW264.7 cells, in which it helped block degradation of inhibitor 
of NF-kappaB. In addition, in vivo studies demonstrated that topical 
administration of MSM at 500-1250 microg/ear resulted in similar inhibitory 
activities in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema. 
Collectively, theses results indicate that MSM inhibits LPS-induced release of 
pro-inflammatory mediators in murine macrophages through downregulation of 
NF-kappaB signaling.