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Exp Ther Med. 2014 Sep;8(3):871-876. Epub 2014 Jun 24.

Toll-like receptor 4 monoclonal antibody attenuates lipopolysaccharide-induced acute lung injury in mice.

Author information

  • 1Department of Critical Care Medicine, Sun Yat-sen Memorial Hospital, University of Sun Yat-sen, Guangzhou, Guangdong 510120, P.R. China.
  • 2Department of Anesthesiology, Sun Yat-sen Memorial Hospital, University of Sun Yat-sen, Guangzhou, Guangdong 510120, P.R. China.

Abstract

Toll-like receptor 4 (TLR4) has an important role in the recognition of lipopolysaccharide (LPS) and in the activation of the inflammatory cascade. In the present study, the effect of TLR4 monoclonal antibody (mAb) on LPS-induced acute lung injury (ALI) was investigated in mice. A total of 45 male BALB/c mice were randomly divided into three groups, namely, the control (group C), sepsis (group S) and pretreatment groups (group P). Mice in group P were intraperitoneally treated with TLR4 mAb 1 h prior to the intraperitoneal administration of LPS. Following treatment with LPS for increasing times periods in groups S and P, the mRNA expression level of TLR4 in the lung tissue and the expression of inflammatory factors in the serum were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. The degree of pulmonary edema, expressed as (wet weight - dry weight)/wet weight, as well as the lung injury scores, observed using a light microscope, were also analyzed. The results demonstrated that intraperitoneal administration of LPS in mice increased the mRNA expression levels of TLR4, the secretion of inflammatory factors in the serum, the degree of pulmonary edema and the lung injury score in a time-dependent manner. However, pretreatment with TLR4 mAb effectively attenuated the increased mRNA expression of TLR4 and the overproduction of inflammatory factors to correct the pulmonary edema and the elevated lung injury score induced by LPS. Therefore, TLR4 plays a critical role in LPS-induced ALI, and the TLR4 mAb decreases the secretion of inflammatory factors and attenuates the degree of pulmonary edema, thereby protecting the lungs from LPS-induced ALI.

KEYWORDS:

Toll-like receptor 4 monoclonal antibody; acute lung injury; lung protection; pulmonary edema; rodents

PMID:
25120616
[PubMed]
PMCID:
PMC4113535
Free PMC Article

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