TNFSF14 inhibits neutrophil extracellular trap formation in neutrophil‐like HL‐60 cells.

Abstract

Tissue injury and infection induce a rapid inflammatory response, in which inflammatory cells, primarily neutrophils, leave the blood vessels and move into the affected tissue. Upon their arrival in this tissue, neutrophils use a variety of methods to kill potential pathogens, including phagocytosis, the generation of reactive oxygen species (ROS) that non‐specifically damage microbes, and formation of neutrophil extracellular traps (NETs) that trap microbes in an anti‐microbial environment. In addition to eliminating potential pathogens, ROS and NETs damage host tissues, promoting a positive feedback loop of tissue damage and inflammation that normally ends during the resolution of inflammation. The resolution of inflammation is associated with the inhibition of neutrophil recruitment and function, as well as induction of neutrophil apoptosis. Previous studies comparing wound healing in wild type and knockout mice found that the cytokine TNFSF14 is necessary for timely resolution of inflammation in mouse wounds, though the mechanism remains unclear. TNFSF14 could promote the resolution of inflammation by reducing cytokine production in the affected tissue, increasing neutrophil apoptosis, and/or reducing pro‐inflammatory neutrophil functions, such as ROS production and NET formation. In this study, we investigated whether TNFSF14 decreases HL‐60 neutrophil‐like cell production of ROS or NETs in response to multiple stimuli, using fluorimetry of DCF‐DA‐stained HL‐60 cells to quantify ROS production and fluorimetry of Sytox Green‐stained extracellular DNA to quantify NET formation. We found that, while TNFSF14 does not inhibit ROS production in these cells, it does decrease NET formation in response to PMA and LPS, suggesting that TNFSF14 may promote the resolution of inflammation through its inhibition of NET formation.Support or Funding InformationResearch start‐up and faculty development funding from DePauw UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.