Protective effect of antagonist of high-mobility group box 1 on lipopolysaccharide-induced acute lung injury in mice.
We explored the effects of recombinant A-box (rA-box), a specific blockade for endogenous high mobility group box 1 (HMGB1) protein, on acute lung inflammation induced by lipopolysaccharide (LPS) in vivo. Acute lung injury (ALI) was produced successfully by intratracheal administration of LPS (10 microg/mouse) in male BALB/c mice. rA-box (0.3, 0.6 mg/mouse, i.p.) was administered 30 min prior to or 2 h after LPS exposure. Bronchoalveolar lavage fluid (BALF) was obtained to measure chemokines, proinflammatory cytokines, total cell counts and proteins at the indicated time points. It was found that rA-box caused a significant reduction in the total cells and neutrophils in BALF, a significant reduction in the W/D ratio and protein leakage at 24 h after LPS challenge. In addition, rA-box was also believed to have downregulated the expression of LPS-induced chemokines (keratinocyte-derived chemokine) and proinflammatory cytokines, including early mediator TNF-a and late mediator HMGB1. These findings confirm the significant protection of rA-box against LPS-induced ALI, and the effect mechanism of rA-box was associated with decreasing the expression of chemokines and proinflammatory cytokines.
Gong
Q
Q
Department of Immunology, School of Medicine, Yangtze University, Jingzhou, China. gongquan168@yahoo.com.cn
Xu
J-F
JF
Yin
H
H
Liu
S-F
SF
Duan
L-H
LH
Bian
Z-L
ZL
D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D020816:Amino Acid Motifs; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors*; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018925:Chemokines; D024243:HMGB1 Protein; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C074302:keratinocyte-derived chemokines