1,5-Anhydro-D-fructose attenuates lipopolysaccharide-induced cytokine release via suppression of NF-kappaB p65 phosphorylation.
Lipopolysaccharide (LPS) stimulates macrophages by activating NF-kappaB, which contributes to the release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. 1,5-Anhydro-D-fructose (1,5-AF), a monosaccharide formed from starch and glycogen, exhibits anti-oxidant activity and enhances insulin secretion. This study examined the effects of 1,5-AF on LPS-induced inflammatory reactions and elucidated its molecular mechanisms. Before LPS challenge, mice were pretreated with 1,5-AF (38.5 mg/kg). We found that 1,5-AF pretreatment attenuated cytokine release into the serum, including TNF-alpha, IL-6 and macrophage chemoattractant protein (MCP)-1. Furthermore, pretreatment with 1,5-AF (500 microg/ml) attenuated cytokine release, and 1,5-AF directly inhibited the nuclear translocalization of the NF-kappaB p65 subunit in LPS-stimulated murine macrophage-like RAW264.7 cells. This inhibition was responsible for decreased LPS-induced phosphorylation on Ser536 of the NF-kappaB p65 subunit, which is a posttranslational modification involved in the non-canonical pathway. Collectively, these findings indicate that the anti-inflammatory activity of 1,5-AF occurs via inactivation of NF-kappaB.
Meng
Xiaojie
X
Department of Laboratory and Vascular Medicine, Field of Cardiovascular and Respiratory Disorders, Department of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Science, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Kawahara
Ko-ichi
K
Nawa
Yuko
Y
Miura
Naoki
N
Shrestha
Binita
B
Tancharoen
Salunya
S
Sameshima
Hisayo
H
Hashiguchi
Teruto
T
Maruyama
Ikuro
I
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D005632:Fructose; C048927:1,5-anhydrofructose