RGD Reference Report - 15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia. - Rat Genome Database

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15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia.

Authors: Park, EJ  Park, SY  Joe, EH  Jou, I 
Citation: Park EJ, etal., J Biol Chem 2003 Apr 25;278(17):14747-52. Epub 2003 Feb 12.
RGD ID: 1299058
Pubmed: PMID:12584205   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M210819200   (Journal Full-text)

Peroxisome proliferator-activated receptor (PPAR)-gamma 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-gamma agonist-mediated suppression of brain inflammation. We show that 15-deoxy-Delta12,14-prostaglandin J(2) (15d-PGJ(2)) 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-gamma agonist-mediated reduction in phosphorylation leads to the suppression of JAK-STAT-dependent inflammatory responses. The effects of 15d-PGJ(2) and rosiglitazone are not mediated by activation of PPAR-gamma. 15d-PGJ(2) 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-PGJ(2) and rosiglitazone suppress the initiation of JAK-STAT inflammatory signaling independently of PPAR-gamma, thus attenuating brain inflammation.

Objects referenced in this article
Gene Jak1 Janus kinase 1 Rattus norvegicus
Gene Jak2 Janus kinase 2 Rattus norvegicus
Gene Socs1 suppressor of cytokine signaling 1 Rattus norvegicus
Gene Socs3 suppressor of cytokine signaling 3 Rattus norvegicus
Gene Stat1 signal transducer and activator of transcription 1 Rattus norvegicus
Gene Stat3 signal transducer and activator of transcription 3 Rattus norvegicus

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