SOCS1 suppresses IL-1 beta-induced C/EBP beta expression via transcriptional regulation in human chondrocytes

作者：Ha You Jung; Choi Yong Seok; Kang Eun Ha; Shin Kichul; Kim Tae Kyun; Song Yeong Wook; Lee Yun Jong^*

来源：Experimental and Molecular Medicine, 2016, 48(6): e241.

DOI：10.1038/emm.2016.47

CAAT/enhancer-binding protein-beta (C/EBP beta) is a transcription factor that regulates interleukin-1 beta (IL-1 beta)-induced catabolic pathways, including the expression of matrix metalloproteinases (MMPs), in chondrocytes. We previously reported that suppressor of cytokine signaling 1 (SOCS1) inhibits IL-1 beta signaling in chondrocytes. However, the effect of SOCS1 on C/EBP beta has not been explored. To investigate the interaction between SOCS1 and C/EBP beta, we established human SW1353 cells with overexpression or knockdown of SOCS1 or C/EBP beta. Both SOCS1 and C/EBP beta were involved in transcription of MMP-3 and MMP-13. When stimulated with IL-1 beta, C/EBP beta levels were significantly increased by SOCS1 knockdown and decreased by SOCS1 overexpression. A similar change in IL-1 beta-induced C/EBP beta expression was observed in SOCS1-transfected human articular chondrocytes. However, C/EBP beta overexpression or knockdown did not change the levels of IL-1 beta-induced SOCS1. SOCS1 regulated the levels of C/EBP beta mRNA by ubiquitination of C/EBP beta as well as transcriptional regulation. Furthermore, it suppressed the phosphorylation of cAMP response element-binding protein (CREB), an active transcription factor of C/EBP beta. 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/EBP beta to the MMP-13 promoter. Taken together, our results demonstrate that SOCS1 downregulates the p38-CREB-C/EBP beta pathway resulting in increased expression of MMPs in chondrocytes.

• 出版日期2016-6