Lysophosphatidylserine Induces MUC5AC Production via the Feedforward Regulation of the TACE-EGFR-ERK Pathway in Airway Epithelial Cells in a Receptor-Independent Manner

Abstract

Lysophosphatidylserine (LysoPS) is an amphipathic lysophospholipid that mediates a broad spectrum of inflammatory responses through a poorly characterized mechanism. Because LysoPS levels can rise in a variety of pathological conditions, we sought to investigate LysoPS’s potential role in airway epithelial cells that actively participate in lung homeostasis. Here, we report a previously unappreciated function of LysoPS in production of a mucin component, MUC5AC, in the airway epithelial cells. LysoPS stimulated lung epithelial cells to produce MUC5AC via signaling pathways involving TACE, EGFR, and ERK. Specifically, LysoPS- dependent biphasic activation of ERK resulted in TGF-α secretion and strong EGFR phosphorylation leading to MUC5AC production. Collectively, LysoPS induces the expression of MUC5AC via a feedback loop composed of proligand synthesis and its proteolysis by TACE and following autocrine EGFR activation. To our surprise, we were not able to find a role of GPCRs and TLR2, known LyoPS receptors in LysoPS-induced MUC5AC production in airway epithelial cells, suggesting a potential receptor-independent action of LysoPS during inflammation. This study provides new insight into the potential function and mechanism of LysoPS as an emerging lipid mediator in airway inflammation.

Lung Lipidomic Alterations in Beagle Dogs Infected with Toxocara canis

“…TG is hydrolyzed to provide FA for many cellular processes, such as lipid synthesis and energy production [ 27 ]. Additionally, lysophosphatidylserine (LPS) is an amphipathic lysophospholipid, which mediates the inflammatory response [ 28 ]. By studying the role of LPS in airway epithelial cells that were involved in lung homeostasis, it was found that LPS has a potential receptor-independent role during inflammation [ 28 ], which provides new insights for subsequent studies.…”

“…Additionally, lysophosphatidylserine (LPS) is an amphipathic lysophospholipid, which mediates the inflammatory response [ 28 ]. By studying the role of LPS in airway epithelial cells that were involved in lung homeostasis, it was found that LPS has a potential receptor-independent role during inflammation [ 28 ], which provides new insights for subsequent studies. At 96 hpi, LPS was upregulated 1.33 times, including 12 upregulated LPS lipid species.…”

“…At 96 hpi, LPS was upregulated 1.33 times, including 12 upregulated LPS lipid species. LPS is a deacylated form of phosphatidylserine, and is known as an important class of a bioactive glycophospholipid mediator, which has various immunomodulatory functions, primarily on immune cells, especially mast cells [ 28 ]. Studies have shown that elevated LPS concentrations can cause an inflammatory response [ 29 , 30 ].…”