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  • 标题:MiR-146a induction by cyanobacterial lipopolysaccharide antagonist (CyP) mediates endotoxin cross-tolerance
  • 本地全文:下载
  • 作者:Monica Molteni ; Annalisa Bosi ; Vincenzo Saturni
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2018
  • 卷号:8
  • 期号:1
  • 页码:11367
  • DOI:10.1038/s41598-018-29820-w
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:Endotoxin tolerance is a phenomenon characterized by a reduced capacity of monocytes and macrophages to respond to repeated stimulation with lipopolysaccharide (LPS) which has been suggested to represent a way of controlling the intensity and duration of innate immune response. During endotoxin tolerance, monocytes undergo functional re-programming primarily by epigenetic regulation. Recently, micro-RNA (miR)-146a has been demonstrated to be the major player of the negative regulation of the pro-inflammatory response, affecting TNF-α production. In this study, we have employed CyP, a cyanobacterial LPS antagonist acting on TLR4-MD2 complex, for priming human monocytes and evaluating their response to a subsequent challenge with E. coli LPS. Results show that CyP is able to induce cross-tolerance to E. coli LPS by inhibiting TNF-α production. The mechanism of action is mediated by a specific induction of miR-146a and reduction of IRAK1 and TRAF6 expressions in human monocytes by CyP priming. Up-regulation of miR-146a by CyP alone, affects subsequent cell response in term of TNF-α production even when monocytes are incubated with other TLR ligands, as lipoteichoic acid (LTA), thus confirming miR-146a as a critical player mediating TNF-α regulation during cross-tolerance with CyP.
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