NF-кB increases LPS-mediated procalcitonin production in human hepatocytes
Bai Yongfeng, Lu Jun, Cheng Ying, Zhang Feng, Fan Xueyu, Weng Yuanyuan, Zhu Jin
Journal:Scientific Reports
IF:4.12
DOI:10.1038/s41598-018-27302-7
PMID:29891911
Published:2018-06-11
research field:分子生物学免疫学传染病学
Abstract
For years, procalcitonin (PCT) has been employed as a diagnostic biomarker for the severity of sepsis and septic shock, as well as for guiding the application of antibiotics. However, the molecular/cellular basis for the regulation of PCT production is not fully understood. In this study, we identified the signalling pathway by which the expression of PCT was induced by lipopolysaccharide in human hepatocytes at the mRNA and protein levels. This expression was dependent on nuclear transcription factor κB (NF-κB), as indicated by a NF-κB binding site (nt −53 to −44) found in the PCT promoter region. We also showed that microRNA-513b (miR-513b) was also able to bind to the 3′-untranslated region (UTR) of the PCT promoter sequence. Meanwhile, the activation of NF-κB down-regulated the expression of miR-513b. In conclusion, we suggest that NF-κB is capable of enhancing the expression of PCT by either directly activating the transcription of the PCT gene or indirectly modulating the expression of its regulatory component, miR-513b. Our results indicate a molecular mechanism responsible for the regulation of PCT production.
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