PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
ROS-Dependent Activation of EGFR/Akt/p38 MAPK and JNK1/2/FoxO1 and AP-1 Pathways in Human Pulmonary Alveolar Epithelial Cells Leads to Up-Regulation of COX-2/PGE2 Induced by Silica Nanoparticles
Version 1
: Received: 18 August 2023 / Approved: 18 August 2023 / Online: 22 August 2023 (07:37:29 CEST)
How to cite:
Lin, Y.; Yang, C.; Lee, I.; Wu, W.; Lin, C.; Hsiao, L.; Yang, C. ROS-Dependent Activation of EGFR/Akt/p38 MAPK and JNK1/2/FoxO1 and AP-1 Pathways in Human Pulmonary Alveolar Epithelial Cells Leads to Up-Regulation of COX-2/PGE2 Induced by Silica Nanoparticles. Preprints2023, 2023081382. https://doi.org/10.20944/preprints202308.1382.v1
Lin, Y.; Yang, C.; Lee, I.; Wu, W.; Lin, C.; Hsiao, L.; Yang, C. ROS-Dependent Activation of EGFR/Akt/p38 MAPK and JNK1/2/FoxO1 and AP-1 Pathways in Human Pulmonary Alveolar Epithelial Cells Leads to Up-Regulation of COX-2/PGE2 Induced by Silica Nanoparticles. Preprints 2023, 2023081382. https://doi.org/10.20944/preprints202308.1382.v1
Lin, Y.; Yang, C.; Lee, I.; Wu, W.; Lin, C.; Hsiao, L.; Yang, C. ROS-Dependent Activation of EGFR/Akt/p38 MAPK and JNK1/2/FoxO1 and AP-1 Pathways in Human Pulmonary Alveolar Epithelial Cells Leads to Up-Regulation of COX-2/PGE2 Induced by Silica Nanoparticles. Preprints2023, 2023081382. https://doi.org/10.20944/preprints202308.1382.v1
APA Style
Lin, Y., Yang, C., Lee, I., Wu, W., Lin, C., Hsiao, L., & Yang, C. (2023). ROS-Dependent Activation of EGFR/Akt/p38 MAPK and JNK1/2/FoxO1 and AP-1 Pathways in Human Pulmonary Alveolar Epithelial Cells Leads to Up-Regulation of COX-2/PGE2 Induced by Silica Nanoparticles. Preprints. https://doi.org/10.20944/preprints202308.1382.v1
Chicago/Turabian Style
Lin, Y., Li-Der Hsiao and Chuen-Mao Yang. 2023 "ROS-Dependent Activation of EGFR/Akt/p38 MAPK and JNK1/2/FoxO1 and AP-1 Pathways in Human Pulmonary Alveolar Epithelial Cells Leads to Up-Regulation of COX-2/PGE2 Induced by Silica Nanoparticles" Preprints. https://doi.org/10.20944/preprints202308.1382.v1
Abstract
The risk of lung exposure to silica nanoparticles (SiNPs) and related lung inflammatory injury is increasing with the wide application of SiNPs in a variety of industries. A growing body of research has revealed that cyclooxygenase (COX)-2/ prostaglandin E2 (PGE2) up-regulated by SiNPs toxicity has a role during pulmonary inflammation. The detailed mechanisms underlying SiNPs-induced COX-2 expression and PGE2 synthesis remain unknown. The present study aims to dissect the molecular components involved in COX-2/PGE2 up-regulated by SiNPs in human pulmonary alveolar epithelial cells (HPAEpiCs) which are one of the major targets while SiNPs are inhaled. In the present study, we demonstrated that SiNPs induced COX-2 expression and PGE2 release, which were inhibited by pretreatment with a reactive oxygen species (ROS) scavenger (edaravone) or the inhibitors of proline-rich tyrosine kinase 2 (Pyk2, PF-431396), epidermal growth factor receptor (EGFR, AG1478), phosphatidylinositol 3‑kinase (PI3K, LY294002), protein kinase B (Akt, Akt inhibitor VIII), p38 mitogen-activated protein kinase (MAPK) (p38 MAPK inhibitor VIII), c-Jun N-terminal kinases (JNK)1/2 (SP600125), Forkhead Box O1 (FoxO1, AS1842856), and activator protein 1 (AP-1, Tanshinone IIA). In addition, we also found that SiNPs induced ROS-dependent Pyk2, EGFR, Akt, p38 MAPK, and JNK1/2 activation in these cells. These signaling pathways induced by SiNPs could further cause c-Jun and FoxO1 activation and translocation from the cytosol to the nucleus. AP-1 and FoxO1 activation could increase COX-2 and PGE2 levels induced by SiNPs. Finally, the COX-2/PGE2 axis might promote the inflammatory responses in HPAEpiCs. In conclusion, we suggested that SiNPs induced COX-2 expression accompanied by PGE2 synthesis mediated via ROS/Pyk2/EGFR/PI3K/Akt/p38 MAPK- and JNK1/2-dependent FoxO1 and AP-1 activation in HPAEpiCs.
Medicine and Pharmacology, Pulmonary and Respiratory Medicine
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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