15-deoxy-delta (12,14)-PGJ2 inhibits astrocyte IL-1 signaling: inhibition of NF-kappaB and MAP kinase pathways and suppression of cytokine and chemokine expression.
We studied the role of 15-deoxy-delta (12,14)-PGJ2 (15d-PGJ2), a macrophage inhibitor with reported therapeutic effects on experimental allergic encephalomyelitis, in human astrocyte activation in vitro. 15d-PGJ2 inhibited a broad range of astrocyte inflammatory gene expression induced by IL-1, including cytokines (TNFalpha and IL-6), chemokines (RANTES/CCL5 and IP-10/CXCL10) and inducible nitric oxide synthase. 15d-PGJ2 inhibited transactivation of NF-kappaB-dependent promoters, as well as p38 and JNK MAPK phosphorylation induced by IL-1, while having no inhibitory effect on IFN-induced Stat signaling pathways. Our results demonstrating 15d-PGJ2-mediated astrocyte deactivation through inhibition of NF-kappaB are similar to those described for macrophages, and add astrocytes as additional targets for this prostaglandin (PG).
Zhao
Meng-Liang
ML
Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Brosnan
Celia F
CF
Lee
Sunhee C
SC
D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D013997:Time Factors
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D018925:Chemokines; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D007155:Immunologic Factors; D007375:Interleukin-1; D016328:NF-kappa B; D009573:Nitrites; D015230:Prostaglandin D2