Role of EP4 prostaglandin E2 receptor in the ischemic liver

2005 ◽  
Vol 37 (1) ◽  
pp. 422-424 ◽  
Author(s):  
Y. Kuzumoto ◽  
M. Sho ◽  
N. Ikeda ◽  
T. Mizuno ◽  
K. Hamada ◽  
...  
2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A.T Takakuma ◽  
M.N Nishii ◽  
R.S Saji ◽  
K.S Sakai ◽  
R.M Matsumura ◽  
...  

Abstract Background Prostaglandin E2 receptor 4 (EP4) plays a crucial role in inflammatory diseases. Inflammatory cardiomyopathy often leads to refractory heart failure. Purpose We aimed to evaluate the role of EP4 in the development of inflammatory cardiomyopathy. Methods Experimental autoimmune myocarditis (EAM) was induced by immunization with cardiac myosin in balb/c mice. EP4 selective antagonist (CJ-42794, Cayman Chemical: 30 mg/kg/day), EP4 selective agonist (20 mg/kg/day), both, or vehicle alone was daily administrated after the immunization. Cardiac function and dimensions were assessed by echocardiography. Blood pressure and heart rate were assessed with tail-cuff method. Cardiac inflammation and fibrosis were immunohistologically examined. Molecular examination was performed by RT-PCR and immunoblotting. Results Cardiac dysfunction and dilatation were worsened on day 21 in EP4 antagonist-treated group compared with in the vehicle-treated group, accompanied by an increase in cellular infiltration area (21.7±1.9 vs. 11.0±2.7%, P=0.0367, respectively). Conversely, cardiac dysfunction and dilatation were improved in EP4 agonist-treated group compared with in the vehicle-treated group (Left ventricular fractional shortening: 69±3% vs. 40±4%, P<0.0001; Left ventricular systolic dimension: 0.7±0.1mm vs. 1.9±0.3mm, P=0.0007; respectively). These parameters did not show significant differences between both-treated group and the vehicle-treated group. The protective effect of EP4 stimulation in EAM was also kept on day 56. Moreover, cardiac fibrosis area as well as mRNA expressions of Type III collagen and brain natriuretic peptide in the bulk hearts was significantly reduced on day 56 in EP4 agonist-treated group compared with in the vehicle-treated group (12.3±2.4% vs. 24.7±3.0%, P=0.0278, respectively). Cardiac expression of phosphorylated smad 2/3 protein as well as TGF-β1 mRNA did not show significant differences between the 2 groups, while cardiac expression of RORgammat protein, the master regulator of Th17 immunity was increased in the EP4 antagonist-treated group. Conclusions EP4 activation negatively regulated the induction of cardiac autoimmunity, which alleviated cardiac dysfunction, dilatation, and fibrosis. EP4 may be a therapeutic target for preventing the development of inflammatory cardiomyopathy. FUNDunding Acknowledgement Type of funding sources: None.


2014 ◽  
Vol 23 (1) ◽  
pp. 163-169 ◽  
Author(s):  
Xiao-Yi Jia ◽  
Yan Chang ◽  
Xiao-Jing Sun ◽  
Xing Dai ◽  
Wei Wei

2020 ◽  
Author(s):  
Hyeogsun Kwon ◽  
David R. Hall ◽  
Ryan C. Smith

AbstractLipid-derived signaling molecules known as eicosanoids have integral roles in mediating immune and inflammatory processes across metazoans. This includes the function of prostaglandins and their cognate G protein-coupled receptors (GPCRs) to employ their immunological actions. In insects, prostaglandins have been implicated in the regulation of both cellular and humoral immune responses, yet studies have been limited by the absence of a described prostaglandin receptor. Here, we characterize a prostaglandin E2 receptor (AgPGE2R) in the mosquito Anopheles gambiae and examine its contributions to innate immunity. AgPGE2R expression is most abundant in circulating hemocytes where it is primarily localized to oenocytoid immune cell populations. Through the administration of prostaglandin E2 (PGE2) and AgPGE2R-silencing by RNAi, we demonstrate that PGE2 signaling regulates the expression of a subset of prophenoloxidases (PPOs) and antimicrobial peptides (AMPs). PGE2 priming via the AgPGE2R significantly limited bacterial replication and suppressed Plasmodium oocyst survival. Additional experiments establish that PGE2 priming increases phenoloxidase (PO) activity through the increased expression of PPO1 and PPO3, which significantly influence Plasmodium oocyst survival. We also provide evidence that PGE2 priming is concentration-dependent, where high concentrations of PGE2 promote oenocytoid lysis, negating the protective effects of PGE2 priming on anti-Plasmodium immunity. Taken together, our results characterize the AgPGE2R and the role of prostaglandin signaling on immune cell function, providing new insights into the role of PGE2 on anti-bacterial and anti-Plasmodium immune responses in the mosquito host.


Toxicology ◽  
2019 ◽  
Vol 415 ◽  
pp. 10-17
Author(s):  
Keiko Aida-Yasuoka ◽  
Noriko Nishimura ◽  
Nozomi Fujisawa ◽  
Nozomi Endo ◽  
Shuh Narumiya ◽  
...  

2015 ◽  
Vol 46 ◽  
pp. 293-310 ◽  
Author(s):  
Xiaochun Zhao ◽  
Tao Wu ◽  
Che-Feng Chang ◽  
He Wu ◽  
Xiaoning Han ◽  
...  

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