STAT1 regulates MD-2 expression in monocytes of sepsis via miR-30a.

Abstract

Sepsis is a major cause of morbidity and mortality in critically ill patients. MD-2 is a 25-kDa lipopolysaccharide (LPS)-binding protein that forms a heterodimer with TLR42, but its regulation in sepsis is not clear. This study aims to investigate the molecular mechanism of regulation of MD-2. Inflammation cytokines in monocytes were analyzed by real-time RT-PCR and ELISA, and it was found that IL-10 was elevated significantly in the monocytes with LPS treatment. And then, when the cells were treated with IL-10, STAT1 was activated in the monocytes using Western blotting. It was also found that STAT1 could enhance MD-2 expression on transcriptional and posttranscriptional levels. Finally, miR-30a was predicted to the molecule that may regulate STAT1 expression. It was verified that STAT1 was a new target gene of miR-30a. miR-30a could inhibit IL-10-induced cytokine release by targeting STAT1-MD-2 in monocytes. In conclusion, this study for the first time demonstrated that miR-30a inhibits MD-2 expression by targeting of STAT1 in human monocytes.

• Authors: Yanhong Wang, Tiehua Li, Benquan Wu, Hui Liu, Jinmei Luo, Dingyun Feng, Yunfeng Shi
• Journal: Inflammation (Inflammation) Vol. 37 Issue 6 Pg. 1903-11 (Dec 2014) ISSN: 1573-2576 [Electronic] United States
• PMID: 24858600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• LY96 protein, human
• Lymphocyte Antigen 96
• MIRN30b microRNA, human
• MicroRNAs
• STAT1 Transcription Factor
• STAT1 protein, human
• Interferon-gamma

Topics

• Cell Line
• Gene Expression Regulation
• Humans
• Interferon-gamma (pharmacology)
• Interleukin-6 (pharmacology)
• Lymphocyte Antigen 96 (biosynthesis)
• MicroRNAs (biosynthesis)
• Monocytes (drug effects, metabolism)
• STAT1 Transcription Factor (physiology)
• Sepsis (metabolism)