Dynamic modulation of innate immune response by varying dosages of lipopolysaccharide (LPS) in human monocytic cells.

作者: Matthew C. Morris , Elizabeth A. Gilliam , Julia Button , Liwu Li

DOI: 10.1074/JBC.M114.583518

关键词: MonocyteLipopolysaccharideImmunologyCREBInnate immune systemInflammationProtein kinase BCell cultureBiologyMediator

摘要: Innate monocytes and macrophages can be dynamically programmed into distinct states depending upon the strength of external stimuli. programming may bear significant relevance to pathogenesis resolution human inflammatory diseases. However, systems analyses with regard dynamic innate leukocytes are lacking. In this study, we focused on responses promonocytic THP-1 cells lipopolysaccharide (LPS). We observed that varying dosages LPS differentially modulate expression selected pro- anti- mediators such as IL-6 IL-33. Super-low preferentially induced pro-inflammatory mediator IL-6, while higher both Mechanistically, demonstrated super-low high doses cause differential activation GSK3 Akt, well transcription factors FoxO1 CREB. Inhibition enabled express IL-33 when challenged dose LPS. On other hand, CREB adenosine suppressed expression. Taken together, our study reveals a modulation monocytic in response endotoxin, shed light understanding balance controls

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