Exp Mol Med.
2016 Jun;48(6):e241. 10.1038/emm.2016.47.
SOCS1 suppresses IL-1β-induced C/EBPβ expression via transcriptional regulation in human chondrocytes
- Affiliations
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- 1Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. yn35@snu.ac.kr
- 2Department of Internal Medicine, Seoul National University Borame Medical Center, Seoul, Korea.
- 3Department of Orthopedic Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
- 4Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
- 5WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Institute, Seoul National University College of Medicine, Seoul, Korea.
- 6Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
- KMID: 2361528
- DOI: http://doi.org/10.1038/emm.2016.47
Abstract
- CAAT/enhancer-binding protein-beta (C/EBPβ) is a transcription factor that regulates interleukin-1β (IL-1β)-induced catabolic pathways, including the expression of matrix metalloproteinases (MMPs), in chondrocytes. We previously reported that suppressor of cytokine signaling 1 (SOCS1) inhibits IL-1β signaling in chondrocytes. However, the effect of SOCS1 on C/EBPβ has not been explored. To investigate the interaction between SOCS1 and C/EBPβ, we established human SW1353 cells with overexpression or knockdown of SOCS1 or C/EBPβ. Both SOCS1 and C/EBPβ were involved in transcription of MMP-3 and MMP-13. When stimulated with IL-1β, C/EBPβ levels were significantly increased by SOCS1 knockdown and decreased by SOCS1 overexpression. A similar change in IL-1β-induced C/EBPβ expression was observed in SOCS1-transfected human articular chondrocytes. However, C/EBPβ overexpression or knockdown did not change the levels of IL-1β-induced SOCS1. SOCS1 regulated the levels of C/EBPβ mRNA by ubiquitination of C/EBPβ as well as transcriptional regulation. Furthermore, it suppressed the phosphorylation of cAMP response element-binding protein (CREB), an active transcription factor of C/EBPβ. In addition, p38 mitogen-activated protein kinases, a target of SOCS1, was involved in CREB phosphorylation. The chromatin immunoprecipitation assay confirmed that SOCS1 overexpression led to reduced binding of C/EBPβ to the MMP-13 promoter. Taken together, our results demonstrate that SOCS1 downregulates the p38-CREB-C/EBPβ pathway resulting in increased expression of MMPs in chondrocytes.
MeSH Terms
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Chondrocytes*
Chromatin Immunoprecipitation
Cyclic AMP Response Element-Binding Protein
Humans*
Matrix Metalloproteinases
p38 Mitogen-Activated Protein Kinases
Phosphorylation
RNA, Messenger
Transcription Factors
Ubiquitin
Ubiquitination
Cyclic AMP Response Element-Binding Protein
Matrix Metalloproteinases
RNA, Messenger
Transcription Factors
Ubiquitin
p38 Mitogen-Activated Protein Kinases
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