脂多糖
支气管肺泡灌洗
急性呼吸窘迫综合征
血管通透性
肺
二肽基肽酶-4
炎症
免疫学
细胞因子
医学
化学
内分泌学
内科学
2型糖尿病
糖尿病
作者
Shunichi Sato,Takeshi Kawasaki,Ryo Hatano,Yu Koyanagi,Yukiko Takahashi,Kei Ohnuma,Chikao Morimoto,Steven M. Dudek,Koichiro Tatsumi,Takuji Suzuki
出处
期刊:American Journal of Physiology-lung Cellular and Molecular Physiology
[American Physiological Society]
日期:2024-03-12
标识
DOI:10.1152/ajplung.00392.2022
摘要
Acute respiratory distress syndrome (ARDS) is characterized by dysregulated inflammation and increased permeability of lung microvascular cells. CD26/Dipeptidyl peptidase-4 (DPP4) is a type II membrane protein that is expressed in several cell types and mediates multiple pleiotropic effects. We previously reported that DPP4 inhibition by sitagliptin attenuates lipopolysaccharide (LPS)-induced lung injury in mice. The current study characterized the functional role of CD26/DPP4 expression in LPS-induced lung injury in mice, isolated alveolar macrophages, and cultured lung endothelial cells. In LPS-induced lung injury, inflammatory responses (bronchoalveolar lavage fluid (BALF) neutrophil numbers and several pro-inflammatory cytokine levels) were attenuated in Dpp4 knockout (Dpp4 KO) mice. However, multiple assays of alveolar capillary permeability were similar between the Dpp4 KO and wild-type mice. TNF-α and IL-6 production was suppressed in alveolar macrophages isolated from Dpp4 KO mice. In contrast, in cultured mouse lung microvascular endothelial cells (MLMVECs), reduction in CD26/DPP4 expression by siRNA resulted in greater ICAM-1 and IL-6 expression after LPS stimulation. Moreover, the LPS-induced vascular monolayer permeability in vitro was higher in MLMVECs treated with Dpp4 siRNA, suggesting that CD26/DPP4 plays a protective role in endothelial barrier function. In summary, this study demonstrated that genetic deficiency of Dpp4 attenuates inflammatory responses but not permeability in LPS-induced lung injury in mice, potentially through differential functional roles of CD26/DPP4 expression in resident cellular components of the lung. CD26/DPP4 may be a potential therapeutic target for ARDS and warrants further exploration to precisely identify the multiple functional effects of CD26/DPP4 in ARDS pathophysiology.
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