Paper
15d-PGJ2 and Rosiglitazone Suppress Janus Kinase-STAT Inflammatory Signaling through Induction of Suppressor of Cytokine Signaling 1 (SOCS1) and SOCS3 in Glia*
Published Apr 25, 2003 · E. Park, Soo Young Park, E. Joe
The Journal of Biological Chemistry
232
Citations
11
Influential Citations
Abstract
Peroxisome proliferator-activated receptor (PPAR)-γ agonists are now emerging as therapeutic drugs for various inflammatory diseases. However, their molecular mechanism of action remains to be elucidated. Here we report a novel mechanism that underlies the PPAR-γ agonist-mediated suppression of brain inflammation. We show that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and rosiglitazone reduce the phosphorylation of STAT1 and STAT3 as well as Janus kinase 1 (JAK1) and JAK2 in activated astrocytes and microglia. The PPAR-γ agonist-mediated reduction in phosphorylation leads to the suppression of JAK-STAT-dependent inflammatory responses. The effects of 15d-PGJ2 and rosiglitazone are not mediated by activation of PPAR-γ. 15d-PGJ2 and rosiglitazone rapidly induce the transcription of suppressor of cytokine signaling (SOCS) 1 and 3, which in turn inhibit JAK activity in activated glial cells. In addition, Src homology 2 domain-containing protein phosphatase 2 (SHP2), another negative regulator of JAK activity, is also involved in their anti-inflammatory action. Our data suggest that 15d-PGJ2 and rosiglitazone suppress the initiation of JAK-STAT inflammatory signaling independently of PPAR-γ, thus attenuating brain inflammation.
15d-PGJ2 and rosiglitazone suppress brain inflammation by inducing suppressor of cytokine signaling (SOCS) 1 and 3, independent of PPAR- activation.
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