Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-kappaB activation.
Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-alpha-evoked translocation of nuclear factor (NF)-kappaB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-kappaB and production of TNF-alpha in mouse macrophage RAW264.7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-alpha level and inhibited the LPS-evoked nuclear translocation of NF-kappaB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS.
Tanaka
S
S
Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kusunoki-Cho, Hyogo, Japan.
Nishiumi
S
S
Nishida
M
M
Mizushina
Y
Y
Kobayashi
K
K
Masuda
A
A
Fujita
T
T
Morita
Y
Y
Mizuno
S
S
Kutsumi
H
H
Azuma
T
T
Yoshida
M
M
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007668:Kidney; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D010837:Vitamin K 1 / Q000494:pharmacology / Q000627:therapeutic use; D024482:Vitamin K 2 / Q000494:pharmacology / Q000627:therapeutic use; D024483:Vitamin K 3 / Q000494:pharmacology / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D024482:Vitamin K 2; D024483:Vitamin K 3; D010837:Vitamin K 1