SOCS1 suppresses IL-1β-induced C/EBPβ expression via transcriptional regulation in human chondrocytes.
- Author:
You Jung HA
1
;
Yong Seok CHOI
;
Eun Ha KANG
;
Kichul SHIN
;
Tae Kyun KIM
;
Yeong Wook SONG
;
Yun Jong LEE
Author Information
- Publication Type:Original Article
- MeSH: Chondrocytes*; Chromatin Immunoprecipitation; Cyclic AMP Response Element-Binding Protein; Humans*; Matrix Metalloproteinases; p38 Mitogen-Activated Protein Kinases; Phosphorylation; RNA, Messenger; Transcription Factors; Ubiquitin; Ubiquitination
- From:Experimental & Molecular Medicine 2016;48(6):e241-
- CountryRepublic of Korea
- Language:English
- 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.
