Abstract
15-Deoxy-Delta(12,14)-prostaglandin J(2) (dPGJ(2)) is a metabolite of prostaglandin D(2), that binds to peroxisome proliferator-activated receptor gamma (PPARgamma). PPARgamma and prostaglandin D(2) synthase, which is required for dPGJ(2) synthesis, are predominantly expressed in macrophages. In contrast, IL-10 and IL-12 produced by macrophages stimulate Th1 and Th2 immune response, respectively. This study investigated the effect of dPGJ(2) on IL-10 and IL-12 production by macrophages in response to lipopolysaccharide (LPS). Our data clearly demonstrated that dPGJ(2) inhibits LPS-induced IL-10 and IL-12 production by macrophages. A different agonist of PPARgamma, 13-hydroxyoctadecadienoic acid, similarly inhibited the production of IL-10 and IL-12 in response to LPS. Further, dPGJ(2) did not appear to act through the PGD(2) receptor. These results suggest that dPGJ(2) may inhibit LPS-induced IL-10 and IL-12 production by macrophages through PPARgamma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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In Vitro Techniques
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Interleukin-10 / biosynthesis*
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Interleukin-12 / biosynthesis*
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Linoleic Acids / pharmacology
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Lipopolysaccharides / pharmacology
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Macrophages, Peritoneal / drug effects*
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Macrophages, Peritoneal / immunology*
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Macrophages, Peritoneal / metabolism
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Male
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Prostaglandin D2 / analogs & derivatives
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Prostaglandin D2 / pharmacology*
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Rats
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Rats, Wistar
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Receptors, Cytoplasmic and Nuclear / agonists
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Immunologic*
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Receptors, Prostaglandin / drug effects
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Receptors, Prostaglandin / metabolism
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Transcription Factors / agonists
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Transcription Factors / metabolism
Substances
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15-deoxy-delta(12,14)-prostaglandin J2
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Linoleic Acids
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Lipopolysaccharides
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Receptors, Cytoplasmic and Nuclear
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Receptors, Immunologic
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Receptors, Prostaglandin
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Transcription Factors
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Interleukin-10
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Interleukin-12
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13-hydroxy-9,11-octadecadienoic acid
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Prostaglandin D2
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prostaglandin D2 receptor