Human ApoA-I overexpression diminishes LPS-induced systemic inflammation and multiple organ damage in mice.
Apolipoprotein A-I (ApoA-I) is the major apolipoprotein of high density lipoprotein (HDL). To investigate the protective effect of ApoA-I against lipopolysaccharide (LPS)-induced systemic inflammation and multiple organ damage in mice, we established a human ApoA-I overexpression mouse model using recombinant adenovirus vector (AdV-AI). The histomorphologic analysis showed that AdV-AI administration greatly attenuated LPS-induced acute injury in lung and kidney. AdV-AI treatment also significantly inhibited LPS-induced increments of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta levels in serum (P < 0.01, P < 0.05 and P < 0.05, respectively) and in bronchoalverolar lavage fluid (P < 0.05, respectively), and of serum creatine kinase and creatinine levels (P < 0.05, respectively). Moreover, we found that the increments of CD14 expression in liver and lung induced by LPS were significantly reduced by AdV-AI treatment (P < 0.05 and P < 0.01, respectively). In conclusion, adenovirus-mediated ApoA-I overexpression plays a protective effect against LPS-induced systemic inflammation and multiple organ damage in mice. Such effect may attribute partly to the suppression of inflammatory cytokine release and reduction of CD14 expression.
Li
Yue
Y
Department of Biochemistry, School of Pharmacy, Fudan University, Shanghai 200032, China.
Dong
Ji-Bin
JB
Wu
Man-Ping
MP
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009102:Multiple Organ Failure / Q000517:prevention & control*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016632:Apolipoprotein A-I; D053583:Interleukin-1beta; D015850:Interleukin-6; D008055:Lipids; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha