Anti- and proinflammatory effects of 15-deoxy-delta-prostaglandin J2(15d-PGJ2) on human eosinophil functions.
The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is recognized as a potent lipid mediator that is derived from PGD(2), which is produced abundantly in allergic inflammatory sites. It is now established that 15d-PGJ(2) negatively regulates cellular functions through its intracellular targets such as peroxisome proliferator-activated receptor-gamma (PPARgamma). However, recent studies revealed that 15d-PGJ(2) appears to possess not only anti-inflammatory activities but also a proinflammatory potential depending on its concentration and the activation state of the target cell. For instance, at low concentrations, 15d-PGJ(2) enhances eotaxin-induced chemotaxis, shape change, and actin reorganization in eosinophils through its ligation with PPARgamma. Moreover, 15d-PGJ(2) itself is a potent chemoattractant, and it induces calcium mobilization, and up-regulates CD11b expression through its membrane receptor--chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Conversely, at high concentrations, 15d-PGJ(2) inhibits eosinophil survival by inducing apoptosis in a PPARgamma-independent manner. Here, we discuss the pathophysiological roles of 15d-PGJ(2) that could act as a paracrine, autocrine, and intracrine substance to regulate eosinophil functions.
Ueki
Shigeharu
S
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Akita, Japan.
Kato
Hikari
H
Kobayashi
Yoshiki
Y
Ito
Wataru
W
Adachi
Tetsuya
T
Nagase
Hiroyuki
H
Ohta
Ken
K
Kayaba
Hiroyuki
H
Chihara
Junichi
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication / Q000502:physiology; D039481:CD11b Antigen / Q000096:biosynthesis / Q000235:genetics; D020013:Calcium Signaling / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D047495:PPAR gamma / Q000819:agonists / Q000502:physiology; D019899:Paracrine Communication / Q000502:physiology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D011982:Receptors, Prostaglandin / Q000502:physiology
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D039481:CD11b Antigen; D047495:PPAR gamma; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor