G protein‐coupled estrogen receptor agonist G‐1 decreases ADAM10 levels and NLRP3‐inflammasome component activation in response to Staphylococcus aureus alpha‐hemolysin
Staphylococcus aureus
Inflammasomes
THP-1 Cells
Macrophages
Bacterial Toxins
Caspase 1
ADAM10
Membrane Proteins
Dipeptides
GPER
Hydroxamic Acids
Microbiology
QR1-502
Receptors, G-Protein-Coupled
ADAM10 Protein
Hemolysin Proteins
Adenosine Triphosphate
NLRP3
Receptors, Estrogen
inflammasome
alpha‐hemolysin
NLR Family, Pyrin Domain-Containing 3 Protein
Humans
Original Article
Amyloid Precursor Protein Secretases
DOI:
10.1002/mbo3.1423
Publication Date:
2024-06-13T05:09:43Z
AUTHORS (5)
ABSTRACT
AbstractThe G protein‐coupled estrogen receptor, also known as GPER1 or originally GPR30, is found in various tissues, indicating its diverse functions. It is typically present in immune cells, suggesting its role in regulating immune responses to infectious diseases. Our previous studies have shown that G‐1, a selective GPER agonist, can limit the pathogenesis mediated by Staphylococcus aureus alpha‐hemolysin (Hla). It aids in clearing bacteria in a mouse skin infection model and restricts the surface display of the Hla receptor, ADAM10 (a disintegrin and metalloprotease 10) in HaCaT keratinocytes. In this report, we delve into the modulation of GPER in human immune cells in relation to the NLRP3 inflammasome. We used macrophage‐like differentiated THP‐1 cells for our study. We found that treating these cells with G‐1 reduces ATP release, decreases the activity of the caspase‐1 enzyme, and lessens cell death following Hla intoxication. This is likely due to the reduced levels of ADAM10 and NLRP3 proteins, as well as the decreased display of the ADAM10 receptor in the G‐1‐treated THP‐1 cells. Our studies, along with our previous work, suggest the potential therapeutic use of G‐1 in reducing Hla susceptibility in humans. This highlights the importance of GPER in immune regulation and its potential as a therapeutic target.
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