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Protective Effect of Antagonist of High‐mobility Group Box 1 on Lipopolysaccharide‐Induced Acute Lung Injury in Mice
Author(s) -
Gong Q.,
Xu J.F.,
Yin H.,
Liu S.F.,
Duan L.H.,
Bian Z.L.
Publication year - 2009
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2008.02194.x
Subject(s) - proinflammatory cytokine , hmgb1 , chemokine , lipopolysaccharide , inflammation , immunology , bronchoalveolar lavage , medicine , pharmacology , lung
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 μ g/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.