The effects of CD14 and IL-27 on induction of endotoxin tolerance in human monocytes and macrophages.

The Journal of Biological Chemistry
Carlene PetesKatrina Gee

Abstract

Upon repeated exposure to endotoxin or lipopolysaccharide (LPS), myeloid cells enter a refractory state called endotoxin tolerance as a homeostatic mechanism. In innate immune cells, LPS is recognized by co-receptors Toll-like receptor 4 (TLR4) and CD-14 to initiate an inflammatory response for subsequent cytokine production. One such cytokine, interleukin (IL)-27, is produced by myeloid cells in response to bacterial infection. In monocytes, IL-27 has proinflammatory functions such as up-regulating TLR4 expression for enhanced LPS-mediated cytokine production; alternatively, IL-27 induces inhibitory functions in activated macrophages. This study investigated the effects of IL-27 on the induction of endotoxin tolerance in models of human monocytes compared with macrophages. Our data demonstrate that IL-27 inhibits endotoxin tolerance by up-regulating cell surface TLR4 expression and soluble CD14 production to mediate stability of the surface LPS-TLR4-CD14 complex in THP-1 cells. In contrast, elevated basal expression of membrane-bound CD14 in phorbol 12-myristate 13-acetate (PMA)-THP-1 cells, primary monocytes, and primary macrophages may promote CD14-mediated endocytosis and be responsible for the preservation of an endotoxin-...Continue Reading

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Citations

Nov 30, 2018·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Ali Berkant AvciGerd Rüdiger Burmester
Nov 5, 2019·Frontiers in Oncology·Olena KourkoKatrina Gee
Jul 19, 2019·Clinical Science·Jan Černý, Ilja Stříž
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Aug 17, 2020·The Journal of Biological Chemistry·Timo OosenbrugMaaike E Ressing
May 10, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Rui WangWei Wei

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