Trehalose inhibits inflammatory cytokine production by protecting IkappaB-alpha reduction in mouse peritoneal macrophages.
OBJECTIVE
The aim of this study was to examine whether trehalose, a disaccharide, could inhibit Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS)-enhanced production of inflammatory cytokines in mouse peritoneal macrophages.


METHODS
Mouse peritoneal macrophages were treated with trehalose and stimulated with P. gingivalis LPS. Interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) levels in the culture supernatant were measured by ELISA. The mRNA levels of the cytokines in macrophages were analysed by semi-quantitative RT-PCR. DNA and protein synthesis were measured by incorporation of [(3)H] thymidine or [(14)C] praline into mouse peritoneal macrophages. IkappaB-alpha reductions were assessed by western blot.


RESULTS
Treatment with trehalose suppressed LPS-induced IL-1beta and TNF-alpha production and downregulated transcription of these cytokines. Furthermore, trehalose inhibited LPS-induced reduction of IkappaB-alpha. In addition, we also observed expression of the trehalose receptor (T1R3) in mouse peritoneal macrophages.


CONCLUSIONS
These results may suggest that trehalose inhibits LPS-induced production of IL-1beta and TNF-alpha in mouse peritoneal macrophages by inhibiting degradation of IkappaB-alphavia the trehalose receptor T1R3.
Taya
Kahoru
K
Division of Dental Pharmacology, Department of Oral Medical Science, Ohu University School of Dentistry, Koriyama, Fukushima 963-8611, Japan.
Hirose
Kimiharu
K
Hamada
Setsuo
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects; D015536:Down-Regulation; D020672:I-kappa B Proteins / Q000187:drug effects*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000072000:NF-KappaB Inhibitor alpha; D016966:Porphyromonas gingivalis; D011392:Proline / Q000187:drug effects / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D014199:Trehalose / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C000606205:Nfkbia protein, mouse; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C431926:taste receptors, type 1; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA; D011392:Proline; D014199:Trehalose; D013936:Thymidine