title: Anti- and proinflammatory effects of 15-deoxy-delta-prostaglandin J2(15d-PGJ2) on human eosinophil functions.
abstract: 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.
authors.affiliation: Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Akita, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Ueki
authors.forename: Hikari
authors.initials: H
authors.lastname: Kato
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Wataru
authors.initials: W
authors.lastname: Ito
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Adachi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagase
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kayaba
authors.forename: Junichi
authors.initials: J
authors.lastname: Chihara
mesh_terms: 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
chemical_list: 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