Inhibition of Prostaglandin F<sub>2</sub><sub>α</sub> Receptors Exaggerates HCl-Induced Lung Inflammation in Mice
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 h...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12843 |
| _version_ | 1797507765295382528 |
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| author | Toko Maehara Ko Fujimori |
| author_facet | Toko Maehara Ko Fujimori |
| author_sort | Toko Maehara |
| collection | DOAJ |
| description | 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 PGF<sub>2α</sub> in ALI remains unclear. We aimed to clarify the role of PGF<sub>2α</sub>/PGF<sub>2α</sub> 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. |
| first_indexed | 2024-03-10T04:53:06Z |
| format | Article |
| id | doaj.art-3e631582aee3473abfbe4afc59d66557 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:53:06Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3e631582aee3473abfbe4afc59d665572023-11-23T02:28:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231284310.3390/ijms222312843Inhibition of Prostaglandin F<sub>2</sub><sub>α</sub> Receptors Exaggerates HCl-Induced Lung Inflammation in MiceToko Maehara0Ko Fujimori1Department of Pathobiochemistry, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, JapanDepartment of Pathobiochemistry, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, JapanAcute 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 PGF<sub>2α</sub> in ALI remains unclear. We aimed to clarify the role of PGF<sub>2α</sub>/PGF<sub>2α</sub> 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.https://www.mdpi.com/1422-0067/22/23/12843prostaglandin F<sub>2α</sub> (PGF<sub>2α</sub>)acute lung injury (ALI)lung edema |
| spellingShingle | Toko Maehara Ko Fujimori Inhibition of Prostaglandin F<sub>2</sub><sub>α</sub> Receptors Exaggerates HCl-Induced Lung Inflammation in Mice International Journal of Molecular Sciences prostaglandin F<sub>2α</sub> (PGF<sub>2α</sub>) acute lung injury (ALI) lung edema |
| title | Inhibition of Prostaglandin F<sub>2</sub><sub>α</sub> Receptors Exaggerates HCl-Induced Lung Inflammation in Mice |
| title_full | Inhibition of Prostaglandin F<sub>2</sub><sub>α</sub> Receptors Exaggerates HCl-Induced Lung Inflammation in Mice |
| title_fullStr | Inhibition of Prostaglandin F<sub>2</sub><sub>α</sub> Receptors Exaggerates HCl-Induced Lung Inflammation in Mice |
| title_full_unstemmed | Inhibition of Prostaglandin F<sub>2</sub><sub>α</sub> Receptors Exaggerates HCl-Induced Lung Inflammation in Mice |
| title_short | Inhibition of Prostaglandin F<sub>2</sub><sub>α</sub> Receptors Exaggerates HCl-Induced Lung Inflammation in Mice |
| title_sort | inhibition of prostaglandin f sub 2 sub sub α sub receptors exaggerates hcl induced lung inflammation in mice |
| topic | prostaglandin F<sub>2α</sub> (PGF<sub>2α</sub>) acute lung injury (ALI) lung edema |
| url | https://www.mdpi.com/1422-0067/22/23/12843 |
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