title: 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.affiliation: Department of Medical Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Tiehua
authors.initials: T
authors.lastname: Li
authors.forename: Benquan
authors.initials: B
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Jinmei
authors.initials: J
authors.lastname: Luo
authors.forename: Dingyun
authors.initials: D
authors.lastname: Feng
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Shi
mesh_terms: D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D051218:Lymphocyte Antigen 96 / Q000096:biosynthesis*; D035683:MicroRNAs / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000502:physiology*; D018805:Sepsis / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D007371:Interferon-gamma