15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia
Open accessAbstract
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.
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Rosiglitazone and 15d-PGJ2 can act independently of PPARγ to yield anti-inflammatory effects.
“Park, et al. (2002) demonstrated that rosiglitazone and 15d-PGJ2 can act independently of PPARγ, to yield anti-inflammatory effects [36].”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [36]
Several reports outline an interplay between PPAR and the Janus kinase-STAT (Jak-STAT) system.
“It is important to note that several reports have outlined the interplay between PPAR and the Janus kinase-STAT (Jak-STAT) system [36,82].”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [36]
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References 47 · Cited by 214
- Authors
- Park, E. J., Park, S. Y., Joe, E.-H., & Jou, I.
- Affiliations
- Ajou University (KR)
- Corresponding author
- Jou, Ilo
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-04
- Volume
- 278
- Issue
- 17
- Pages
- 14747-14752
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1968532804
- Cited by
- 214
- References
- 47
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 8 · 2020: 10 · 2019: 7 · 2018: 4 · 2017: 15 · 2016: 9 · 2015: 9 · 2014: 7 · 2013: 8 · 2012: 8
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- AJOU Open Repository (Ajou University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- 15-deoxy-Δ12,14-prostaglandin J2, rosiglitazone, PPARγ agonists, JAK/STAT signaling, SOCS1, SOCS3, SHP2, neuroinflammation, astrocytes, microglia, STAT1 phosphorylation, STAT3 phosphorylation, JAK1, JAK2, anti-inflammatory mechanism
- MeSH terms
- Suppressor of Cytokine Signaling 1 Protein, Suppressor of Cytokine Signaling 3 Protein, Rosiglitazone, Animals, Anti-Inflammatory Agents, Astrocytes, Carrier Proteins, DNA-Binding Proteins, Gene Expression Regulation, Inflammation, Neuroglia, Phosphorylation, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Repressor Proteins, Thiazoles, Transcription Factors, Protein Biosynthesis, Prostaglandin D2, Signal Transduction, Trans-Activators, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear, Thiazolidinediones, STAT1 Transcription Factor, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Rats, Janus Kinase 1, Janus Kinase 2
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