PI3K/AKT and CD40L Signaling Regulate Platelet Activation and Endothelial Cell Damage in Sepsis.

Abstract

Platelets contribute to inflammation and their activation has been suggested as versatile effectors of sepsis. Activation of platelets promotes secretion of CD40L that induces sepsis and multiple organ dysfunction syndrome (MODS). However, the mechanisms regulate platelet-derived CD40L are not fully understood. Activation of PI3K/Akt pathway has been reported as a key component of sepsis, whereas the role of PI3K/Akt pathway in platelet-derived CD40L is unknown. In this study, we identified PI3K/Akt pathway as a key regulator of CD40L secretion by platelets. Significantly, inhibition of PI3K/Akt pathway by Ly294002 attenuated platelet activation and CD40L production. Moreover, PI3K/Akt pathway blocking suppresses vascular endothelial cells in vivo. Furthermore, the expression of biomarkers that represent the severity of sepsis, such as ICAM-1, VCAM-1, and E-selectin, was also suppressed by Ly294002. Altogether, our results confirm the pivotal role of PI3K/Akt pathway in sepsis and its inhibition might be a potential therapeutic target.

• Authors: Peng Wan, Xiang Tan, Yan Xiang, Huasheng Tong, Min Yu
• Journal: Inflammation (Inflammation) Vol. 41 Issue 5 Pg. 1815-1824 (Oct 2018) ISSN: 1573-2576 [Electronic] United States
• PMID: 29956071 (Publication Type: Journal Article)

Chemical References

• Chromones
• Morpholines
• CD40 Ligand
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• CD40 Ligand (metabolism)
• Chromones (pharmacology)
• Endothelial Cells (pathology)
• Humans
• Metabolic Networks and Pathways (drug effects, physiology)
• Morpholines (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Platelet Activation
• Proto-Oncogene Proteins c-akt (metabolism)
• Sepsis (metabolism, pathology)
• Signal Transduction