Fructose-1,6-diphosphate attenuates acute lung injury induced by lipopolysaccharide in mice.
Fructose-1,6-diphosphate (FDP), a high-energy glycolytic pathway intermediate, is reported to have a salutary effect in endotoxic shock and sepsis, but its underlying mechanism of action in inflammation is incompletely understood. In this study, our aim was to examine the function of FDP on acute lung injury (ALI) induced by lipopolysaccharide (LPS). We found that in vitro pretreatment with FDP remarkably repressed the production of TNF-alpha and IL-6 in murine alveolar macrophages MH-S exposed to LPS. In the mouse model of LPS-induced inflammatory lung injury, intravenous precondition of a single 400 mg/kg dose of FDP resulted in a significant reduction in LPS-mediated extravasation of Evans blue dye albumin, bronchoalveolar lavage leucocyte content, and lung tissue myeloperoxidase activity (reflecting phagocyte infiltration). Furthermore, histopathologic examination indicated that alveolitis with inflammatory cells infiltration and alveolar hemorrhage in the alveolar space was less severe in the FDP-treated mice than in the mice treated by LPS alone at 24 h. Additionally, pretreatment with FDP markedly decreased the transcription of TNF-alpha, IL-6 and inducible NO synthase (iNOS), and suppressed the nuclear translocation of NF-kappaB in lung tissues in response to LPS challenge. These results thus suggested that FDP plays an anti-inflammatory role in LPS-mediated acute lung injury, possibly through abrogation of NF-kappaB activation.
Yin
Hui
H
Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Jin
Xiao-Bao
XB
Gong
Quan
Q
Yang
Heng
H
Hu
Li-Yong
LY
Gong
Fei-Li
FL
Zhu
Jia-Yong
JY
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D004195:Disease Models, Animal; D005635:Fructosediphosphates / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D009195:Peroxidase / Q000032:analysis; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects; D000097782:NF-kappaB-Inducing Kinase
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005635:Fructosediphosphates; D015850:Interleukin-6; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase; D017346:Protein Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase; C029063:fructose-1,6-diphosphate