Short Analytical Review
: The anti-inflammatory prostaglandin?
Jose U. Scher
, Michael H. Pillinger
The Division of Rheumatology, New York University School of Medicine, New York, NY 10003, United States
The Hospital for Joint Diseases, New York, NY 10003, United States
The Manhattan VA Hospital of the NY Harbor Healthcare System, New York, NY 10010, United States
Received 26 July 2004; accepted 23 September 2004
Available online 5 November 2004
) is the most recently discovered prostaglandin. This cyclopentanone, the dehydration end
product of PGD
, differs from other prostaglandins in several respects. There is no specific prostaglandin synthase (PGS) leading to 15d-
production and no specific 15d-PGJ
receptor has been identified to date. Instead, 15d-PGJ
has been shown to act via PGD
) and through interaction with intracellular targets. In particular, 15d-PGJ
is recognized as the endogenous ligand for the
intranuclear receptor PPARg. This property is responsible for many of the 15d-PGJ
anti-inflammatory functions. In this review, we
summarize the current understanding of 15d-PGJ
synthesis, biology and main effects both in molecular physiology and pathological states.
D 2004 Elsevier Inc. All rights reserved.
Keywords: Prostaglandin; 15d-PGJ
;PPARg; Inflammation; PGD
; H-PGDS; L-PGDS; NF-nB; Erk
Prostaglandins (PGs) are autacoids synthesized from 20
carbon-containing polyunsaturated fatty acids, principally
arachidonic acid (AA) generated from membrane phospho-
lipids and derived from dietary sources . These eicosa-
-hydroxy-fatty acids) have been detected in
almost every tissue and body fluid. With the exception of
seminal fluid, PGs are not stored in tissues or cells. Instead,
their production may increase in response to diverse stimuli,
and they produce a broad spectrum of biological effects .
PGs contribute to inflammation, smooth muscle tone,
hemostasis, thrombosis, parturition and gastrointestinal
secretion, among others . This review focuses on the
most recently discovered PG, the cyclopentenone 15-deoxy-
). In contrast to most PGs, accumu-
lating data suggests that, at least in some contexts, 15d-PGJ
may exert anti-inflammatory effects.
Synthesis of 15d-PGJ
begins with the sequential
action of three classes of enzymes (Fig. 1). AA generation
phospholipases initially regulates synthesis of all
PGs . However, net levels of PG production are
determined by expression and activity of cyclooxygenases
(COX). COX-1 and COX-2 (also known as PGH synthase
1 and 2) are membrane-related proteins localized to the
inner leaflet of the nuclear envelope and endoplasmic
reticulum bilayers . These bifunctional enzymes first
convert AA into the intermediate PGG
tion), then reduce PGG
by peroxidation to generate PGH
. A complete description of COX characteristics and
biologic mechanisms is beyond the scope of this report.
The reader is referred to several excellent reviews on the
is converted into stable prostanoids by a variety of
specific terminal synthases. Terminal synthases are
1521-6616/$ - see front matter D 2004 Elsevier Inc. All rights reserved.
* Corresponding author. Department of Medicine 630-111j, NY
Harbor Healthcare System, 423 East 23rd Street, New York, NY 10010.
Fax: +1 212 951 3329.
E-mail address: Michael.Pillinger@med.nyu.edu (M.H. Pillinger).
Clinical Immunology 114 (2005) 100 – 109