The anti-inflammatory effect of 10-oxo-trans-11-octadecenoic acid (KetoC) on RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide.

BACKGROUND: There is rapidly developing interest into the role of several anti-inflammatory agents to resolve inflammation in periodontal disease. A bioactive polyunsaturated fatty acid, 10-oxo-trans-11-octadecenoic acid (KetoC), is known to have various beneficial physiological effects; however, the effect of KetoC on inflammation remains unclear. Here, we investigated the effect of KetoC on RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide, and explored the intracellular mechanism responsible for its anti-inflammatory effects. METHODS: RAW 264.7 cells were pre-treated with or without KetoC, and then stimulated with or without P. gingivalis lipopolysaccharide. Levels of tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1ß were determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Specific antagonists for G protein-coupled receptor (GPR)40 and GPR120 were used to clarify the receptor for KetoC. The intracellular mechanism was investigated using western blotting analysis to separate nuclear and cytosolic NF-κB p65 protein. RESULT: KetoC (5 µmol/L) was not toxic to RAW 264.7 cells, and significantly reduced the expression of TNFα and IL-6 mRNA and protein, and IL-1ß mRNA. No protein production of IL-1ß was observed. Additionally, when bound to GPR120, KetoC trended to downregulate nuclear NF-κB p65 protein levels. However, the antagonist for GPR40 failed to diminish the action of KetoC. CONCLUSION: KetoC suppressed the proinflammatory cytokines TNFα, IL-6 and IL-1ß via NF-κB p65, by binding to its receptor GPR120. KetoC is a promising candidate in future studies as a bioactive anti-inflammatory agent in treating periodontal disease.

Neuronal intranuclear hyaline inclusion disease: report of a case and review of the literature.

A case of neuronal intranuclear hyaline inclusion disease (NIHID) is described. The patient was a 26-year-old man who died of a progressive neurologic disorder, the onset of which occurred at the age of 11 years. Clinically, the disease presented as juvenile parkinsonism, and pathologically it was characterized by multiple-system degeneration in conjunction with the ubiquitous presence of intranuclear hyaline inclusions in neurons of the central and peripheral nervous system including the autonomic ganglia. Smaller and less eosinophilic intranuclear inclusions were also present in a small number of glial cells. The neuronal inclusions emitted a strong yellow-green autofluorescence under ultraviolet light and were composed of filaments 10-15 nm in diameter. The glial inclusions also consisted of similar filaments but their autofluorescence could not be determined with certainty because of their small size and background autofluorescence. A review of the literature revealed 19 similar autopsy cases up to 1987. Since the clinical presentation and distribution of neuronal loss as well as the characteristics of the inclusions showed some differences among the cases, some authors speculated that NIHID represented more than one variant of a multiple-system degenerative disease. However, about half of the reported cases had favorable sites of neurodegeneration, such as the pallidum, substantia nigra, motor nuclei of the brain stem, anterior horn cells, Clarke's column and spinal ganglion as well as similarities among the inclusions. Thus, there seems to be a discrete group among cases of NIHID.