2017 journal article

Inhibition of microsomal prostaglandin E-synthase-1 (mPGES-1) selectively suppresses PGE(2) in an in vitro equine inflammation model

VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 192, 33–40.

By: E. Martin  n & S. Jones n 

author keywords: Prostaglandin E-2; Prostaglandin E-synthase; Leukocyte; Anti-inflammatory; NSAID; Horse
MeSH headings : Animals; Blotting, Western / veterinary; Dinoprostone / antagonists & inhibitors; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay / veterinary; Horses; Inflammation / metabolism; Inflammation / physiopathology; Inflammation / veterinary; Leukocytes / metabolism; Microsomes / enzymology; Prostaglandin-E Synthases / antagonists & inhibitors; Prostaglandin-E Synthases / metabolism; Prostaglandin-E Synthases / physiology; Real-Time Polymerase Chain Reaction / veterinary
TL;DR: It is demonstrated that mPGES-1 is a potentially safer and effective therapeutic target for treatment of equine inflammatory disease when compared to traditional non-steroidal anti-inflammatory drugs. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Source: Web Of Science
Added: August 6, 2018

Inhibition of prostaglandin E 2 (PGE 2 ) production effectively limits inflammation in horses, however nonspecific prostaglandin blockade via cyclooxygenase (COX) inhibition elicits deleterious gastrointestinal side effects in equine patients. Thus, more selective PGE 2 targeting therapeutics are needed to treat inflammatory disease in horses. One potential target is microsomal prostaglandin E-synthase-1 (mPGES-1), which is the terminal enzyme downstream of COX-2 in the inducible PGE 2 synthesis cascade. This enzyme has yet to be studied in equine leukocytes, which play a pivotal role in equine inflammatory disease. The objective of this study was to determine if mPGES-1 is a PGE 2 -selective anti-inflammatory target in equine leukocytes. To evaluate this objective, leukocyte-rich plasma (LRP) was isolated from equine whole blood collected via jugular venipuncture of six healthy adult horses of mixed breeds and genders. LRP was primed with granulocyte-monocyte colony-stimulating factor (GM-CSF) and stimulated with lipopolysaccharide (LPS) in the presence or absence of an mPGES-1 inhibitor (MF63), a COX-2 inhibitor (NS-398), or a nonselective COX inhibitor (indomethacin). Following treatment, mPGES-1 and COX-2 mRNA and protein levels were measured via qPCR and western blot, respectively, and PGE 2 , thromboxane (TXA 2 ) and prostacyclin (PGI 2 ) levels were measured in cellular supernatants via ELISA. This study revealed that LPS significantly increased mPGES-1 mRNA, but not protein levels in equine LRP as measured by qPCR and western blot, respectively. In contrast, COX-2 mRNA and protein were coordinately induced by LPS. Importantly, treatment of LPS-stimulated leukocytes with indomethacin and NS-398 significantly reduced extracellular concentrations of multiple prostanoids (PGE 2 , TXA 2 and PGI 2 ), while the mPGES-1 inhibitor MF63 selectively inhibited PGE 2 production only. mPGES-1 inhibition also preserved higher basal levels of PGE 2 production when compared to either COX inhibitor, which might be beneficial in a clinical setting. In conclusion, this work identifies mPGES-1 as a key regulator of PGE 2 production and a PGE 2 -selective target in equine leukocytes. This study demonstrates that mPGES-1 is a potentially safer and effective therapeutic target for treatment of equine inflammatory disease when compared to traditional non-steroidal anti-inflammatory drugs.