An A2Aadenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models

Moore, Christopher C.; Martin, Edward N.; Lee, Grace H.; Obrig, Tom G.; Linden, Joel; Scheld, W. Michael

doi:10.1186/1471-2334-8-141

Cited by 49 publications

(41 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…inflammation (21), acute lung injury (16), and hypoxia (22)), suggesting that A 2A R plays an important role in stress. Consistent with this notion, agonists of A 2A R have been shown to attenuate pathological inflammatory responses (23)(24)(25)(26)(27). Stimulation of A 2A R triggers multiple signaling pathways, including the cAMP-protein kinase A (PKA)-dependent pathway (28), and regulates a wide variety of downstream targets, such as the cAMP-regulated element-binding protein, nuclear factor-B, and hypoxiainducible factor 1, that mediate its effect (29 -31).…”

mentioning

confidence: 83%

The A2A Adenosine Receptor Is a Dual Coding Gene

Lee¹,

Lai

Lee

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

mentioning

confidence: 83%

The A2A Adenosine Receptor Is a Dual Coding Gene

Lee¹,

Lai

Lee

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Therefore, we chose the use of LPS, a common pathogen found in both E. coli and Klebsiella, as a representative pathogen found in cholangitis. Furthermore, in many animal sepsis models, the LPS models show similar trends to models using E. coli (28,34).…”

Section: Discussionmentioning

confidence: 85%

15-Deoxy-Δ^12,14-prostaglandin J₂ prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis

Watanabe

Yokoyama

Kokuryo

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Nakagawa A, Nagino M. 15-Deoxy-⌬ 12,14 -prostaglandin J2 prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis. Am J Physiol Gastrointest Liver Physiol 298: G410 -G418, 2010. First published January 7, 2010 doi:10.1152/ajpgi.00233.2009.-Acute obstructive cholangitis is a common disease with a high mortality rate. Ligands for peroxisome proliferator-activated receptor-␥ (PPAR␥), such as 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15D-PGJ2), have been proposed as a new class of anti-inflammatory compounds. This study investigated the effect of 15D-PGJ2 treatment on lipopolysaccharide (LPS)-induced acute obstructive cholangitis. The rats were randomly assigned to five groups: sham operation (Sham; simple laparotomy), sham operation with intraperitoneal saline infusion (ShamϩSaline), sham operation with intraperitoneal LPS infusion (ShamϩLPS), bile duct ligation (BDL) with saline infusion into the bile duct (BDLϩSaline), and BDL with LPS infusion into the bile duct (BDLϩLPS). Biochemical assays of blood samples, histology of the liver, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were evaluated. Furthermore, the ShamϩLPS and the BDLϩLPS group were divided into two groups (with and without 15D-PGJ2 treatment), and their survival rates were compared. Biochemical assays of blood samples, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were all significantly higher in the BDLϩLPS group compared with those in the BDLϩSaline group, indicating the presence of increased liver damage in the first group. However, preoperative administration of 15D-PGJ2 significantly improved these outcomes. Furthermore, the survival rate after establishment of cholangitis was significantly improved by the administration of 15D-PGJ2 in the BDLϩLPS group. These results clearly demonstrate that 15D-PGJ2 inhibits the inflammatory response and endothelial cell damage seen in acute obstructive cholangitis and could contribute to improve the outcome of this pathology.bile duct ligation; hyaluronic acid clearance; NF-B; portal venous pressure ACUTE OBSTRUCTIVE CHOLANGITIS (AOC) due to infections in the biliary tract is a common occurrence in the clinical setting. Despite recent advances in the treatment of infectious diseases, AOC remains a significant cause of morbidity and mortality. One of the leading reasons for AOC-related death is acute liver failure, which can be triggered by an excessive inflammatory response in the liver. However, the precise mechanism of AOC-induced acute liver failure remains unclear.A number of reports have focused on the role of proinflammatory cytokines, such as tumor necrosis factor-␣ (TNF-␣) and interleukin-6 (IL-6), in the pathophysiology of organ injury from AOC (14). Increases in the levels of these proinflammatory cytokines have been shown to correlate strongly with the severity of multiple organ failure and with the mortality from AOC (12). Ex...

show abstract

“…In this context, compelling evidence supports A 2A receptors as the major immunoregulatory arm of the adenosine system [10]. For this reason, consistent efforts are being dedicated to the development of A 2A receptor agonists for the therapeutic management of several inflammatory disorders, such as asthma [23,24], arthritis [25,26], glomerulonephritis [27,28], sepsis [29,30], and intestinal inflammation [14,31,32]. However, the great expectation about the therapeutic use of A 2A receptor agonists as a viable anti-inflammatory strategy is being challenged by several concerns, mainly depending on their severe hypotensive effects related to the wide distribution of A 2A receptors in the cardiovascular system [33].…”

Section: Discussionmentioning

confidence: 99%

“…For this purpose, a subgroup of animals was treated with test drugs by oral gavage or intraperitoneal route. Systolic blood pressure was measured before euthanization (30,60,120, and 240 min after test drug administration) by the tailcuff method at baseline and after injection of experimental drugs or vehicle (BP recorder 58600; Ugo Basile, Comerio, Italy). An average of three pressure readings was obtained.…”

Section: Evaluation Of the Systemic Effects And Plasma Concentrationsmentioning

confidence: 99%

Anti-inflammatory effect of a novel locally acting A2A receptor agonist in a rat model of oxazolone-induced colitis

Antonioli

El‐Tayeb

Pellegrini

et al. 2017

Purinergic Signalling

View full text Add to dashboard Cite

Adenosine represents a powerful modulating factor, which has been shown to orchestrate the scope, duration, and remission of the inflammatory response through the activation of four specific receptors, classified as A 1 , A 2A , A 2B , and A 3 , all being widely expressed in a variety of immune cells. Several selective A 2A receptor agonists have displayed anti-inflammatory effects, through the suppression of IL-12, TNF, and IFN-γ production by monocytes and lymphocytes, in the setting of chronic intestinal inflammation. However, the therapeutic application of A 2A receptor agonists remains hindered by the risk of serious cardiovascular adverse effects arising from the wide systemic distribution of A 2A receptors. The present study focused on evaluating the antiinflammatory effects of the novel poorly absorbed A 2A receptor agonist PSB-0777 in a rat model of oxazolone-induced colitis as well as to evaluate its cardiovascular adverse effects, paying particular attention to the onset of hypotension, one of the main adverse effects associated with the systemic pharmacological activation of A 2A receptors. Colitis was associated with decreased body weight, an enhanced microscopic damage score and increased levels of colonic myeloperoxidase (MPO). PSB-0777, but not dexamethasone, improved body weight. PSB-0777 and dexamethasone ameliorated microscopic indexes of inflammation and reduced MPO levels. The beneficial effects of PSB-0777 on inflammatory parameters were prevented by the pharmacological blockade of A 2A receptors. No adverse cardiovascular events were observed upon PSB-0777 administration. The novel A 2A receptor agonist PSB-0777 could represent the base for the development of innovative pharmacological entities able to act in an event-specific and site-specific manner.

show abstract

An A2Aadenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models

Abstract: Background: The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A 2A adenosine receptor (AR) agonist treated and untreated animals during experimental sepsis.

Cited by 49 publications

References 38 publications

The A2A Adenosine Receptor Is a Dual Coding Gene

The A2A Adenosine Receptor Is a Dual Coding Gene

15-Deoxy-Δ^12,14-prostaglandin J₂ prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis

Anti-inflammatory effect of a novel locally acting A2A receptor agonist in a rat model of oxazolone-induced colitis

Contact Info

Product

Resources

About

An A2Aadenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models

Abstract: Background: The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A 2A adenosine receptor (AR) agonist treated and untreated animals during experimental sepsis.

Cited by 49 publications

References 38 publications

The A2A Adenosine Receptor Is a Dual Coding Gene

The A2A Adenosine Receptor Is a Dual Coding Gene

15-Deoxy-Δ12,14-prostaglandin J2 prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis

Anti-inflammatory effect of a novel locally acting A2A receptor agonist in a rat model of oxazolone-induced colitis

Contact Info

Product

Resources

About

15-Deoxy-Δ^12,14-prostaglandin J₂ prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis