The effects of CD14 and IL-27 on induction of endotoxin tolerance in human monocytes and macrophages.
J Biol Chem
; 293(45): 17631-17645, 2018 11 09.
Article
en En
| MEDLINE
| ID: mdl-30242126
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-tolerized state in the presence of IL-27. Overall, the efficacy of IL-27 in inhibiting endotoxin tolerance in human THP-1 monocytes and PMA-THP-1 macrophages is affected by membrane-bound and soluble CD14 expression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Monocitos
/
Lipopolisacáridos
/
Interleucinas
/
Modelos Inmunológicos
/
Receptores de Lipopolisacáridos
/
Tolerancia Inmunológica
/
Macrófagos
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2018
Tipo del documento:
Article
País de afiliación:
Canadá