Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory disorders that are caused by aspiration, sepsis, trauma, and pneumonia. A clinical feature of ALI/ARDS is the acute onset of severe hypoxemia, and the mortality rate, which is estimated at 38–50%, remains high. Although prostaglandins (PGs) are detected in the bronchoalveolar lavage fluid of patients with ALI/ARDS, the role of PGF2α in ALI remains unclear. We aimed to clarify the role of PGF2α/PGF2α receptor (FP) signaling in acid-induced ALI using an FP receptor antagonist, AL8810. Intratracheal injection of hydrochloric acid (HCl) increased neutrophil migration into the lungs, leading to respiratory dysfunction. Pre-administration of AL8810 further increased these features. Moreover, pre-treatment with AL8810 enhanced the HCl-induced expression of pro-inflammatory cytokines and neutrophil migratory factors in the lungs. Administration of HCl decreased the gene expression of lung surfactant proteins, which was further reduced by co-administration of AL8810. Administration of AL8810 also increased lung edema and reduced mRNA expression of epithelial sodium channel in the lungs, indicating that AL8810 reduced fluid clearance. Furthermore, AL8810 also increased lipopolysaccharide-induced expression of adhesion molecules such as intracellular adhesion molecule-1 and E-selectin in human umbilical vein endothelial cells. These results indicate that inhibition of FP receptors by AL8810 exacerbated HCl-induced ALI.
Highlights
AL8810 increased the LPS-induced gene expression of intracellular adhesion molecule-1 (ICAM-1) and E-selectin in Human umbilical vein endothelial cells (HUVECs) (Figure 6). These results indicate that inhibition of FP receptors in the vascu(Figure 6). These results indicate that inhibition of FP receptors in the vaslar endothelium increased the expression of molecular adhesion factors, which promoted cular endothelium increased the expression of molecular adhesion factors, which proneutrophil migration into the lungs
We showed that inhibition of FP receptors increased the gene expression of pro-inflammatory mediators, neutrophil migration into bronchoalveolar lavage fluid (BALF), and lung edema in hydrochloric acid (HCl)-administered mice
This is the first report that prostaglandin F2α (PGF2α) /FP signaling is important in regulating the progression of HCl-induced Acute lung injury (ALI)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Coronavirus disease 2019 (COVID-19), has rapidly evolved into a global pandemic [1]. The number of patients with COVID-19 is over 100 million, and 5 million people have died in just 3 years. Research on and development of therapeutic agents and vaccines against COVID-19 are progressing [2]. Further research regarding the pathogenesis of COVID-19 and the development of treatments is indispensable. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)
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