Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS‐independent activation of NF‐κB
Tóm tắt
Reactive oxygen species (ROS) generated by the cellular NADPH‐oxidase are crucial for phagocytic killing of ingested microbes and have been implicated as signaling molecules in various processes. For example, ROS are thought to be involved in activation of the transcription factor NF‐κB, central for mediating production of proinflammatory cytokines in response to inflammatory stimuli. Several studies have demonstrated that inhibitors of the NADPH‐oxidase interfere with NF‐κB activation and production of proinflammatory cytokines. Curiously, patients with chronic granulomatous disease (CGD), an immunodeficiency characterized by an inability to produce ROS, are not only predisposed to severe infections, but also frequently develop various inflammatory complications indicative of exaggerated inflammatory responses. Here, we show that human CGD leukocytes display a hyperinflammatory phenotype with increased production of proinflammatory cytokines in response to stimulation with Toll‐like receptor agonists. The hyperinflammatory phenotype was also evident in mononuclear cells from CGD mice (gp91phox
Từ khóa
Tài liệu tham khảo
Kasahara Y., 1997, Involvement of reactive oxygen intermediates in spontaneous and CD95 (Fas/APO‐1)‐mediated apoptosis of neutrophils., Blood, 89, 1748, 10.1182/blood.V89.5.1748