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Protective Role of Proton-Sensing TDAG8 in Lipopolysaccharide-Induced Acute Lung Injury.

International journal of molecular sciences (2015-12-23)
Hiroaki Tsurumaki, Chihiro Mogi, Haruka Aoki-Saito, Masayuki Tobo, Yosuke Kamide, Masakiyo Yatomi, Koichi Sato, Kunio Dobashi, Tamotsu Ishizuka, Takeshi Hisada, Masanobu Yamada, Fumikazu Okajima
ABSTRACT

Acute lung injury is characterized by the infiltration of neutrophils into lungs and the subsequent impairment of lung function. Here we explored the role of TDAG8 in lung injury induced by lipopolysaccharide (LPS) administrated intratracheally. In this model, cytokines and chemokines released from resident macrophages are shown to cause neutrophilic inflammation in the lungs. We found that LPS treatment increased TDAG8 expression in the lungs and confirmed its expression in resident macrophages in bronchoalveolar lavage (BAL) fluids. LPS administration remarkably increased neutrophil accumulation without appreciable change in the resident macrophages, which was associated with increased penetration of blood proteins into BAL fluids, interstitial accumulation of inflammatory cells, and damage of the alveolar architecture. The LPS-induced neutrophil accumulation and the associated lung damage were enhanced in TDAG8-deficient mice as compared with those in wild-type mice. LPS also increased several mRNA and protein expressions of inflammatory cytokines and chemokines in the lungs or BAL fluids. Among these inflammatory mediators, mRNA and protein expression of KC (also known as CXCL1), a chemokine of neutrophils, were significantly enhanced by TDAG8 deficiency. We conclude that TDAG8 is a negative regulator for lung neutrophilic inflammation and injury, in part, through the inhibition of chemokine production.

MATERIALS
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Product Description

Sigma-Aldrich
Lipopolysaccharides from Escherichia coli O111:B4, γ-irradiated, BioXtra, suitable for cell culture