15-Deoxy-Δ (12,14)-PGJ2 inhibits astrocyte IL-1 signaling: Inhibition of NF-κB and MAP kinase pathways and suppression of cytokine and chemokine expression

We studied the role of 15-deoxy-Δ (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 (TNFα and IL-6), chemokines (RANTES/CCL5 and IP-10/CXCL10) and inducible nitric oxide synthase. 15d-PGJ2 inhibited transactivation of NF-κB-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-κB are similar to those described for macrophages, and add astrocytes as additional targets for this prostaglandin (PG).