Role of rhIL-17 in regulating the mitochondrial pathway proteins in peripheral blood neutrophils.

Abstract

IL-17, classified as an inflammatory cytokine, plays a key role in the activation of inflammatory processes involving neutrophils. Twenty healthy voluntary blood donors were controlled in the study. The granulocyte suspensions were stimulated with rhIL-17 and fMLP. Expression of Bcl-xl, Smac/DIABLO, and Omi/HtrA2 in neutrophil lysates were assessed by Western blot. The level of cytochrome c and activity of caspase 9 was also assayed in these cells. The results of existing research highlight the importance of rhIL-17 in reducing the survival of neutrophils via the mitochondria, depending on the Bcl-2 protein family. Our research has indicated that rhIL-17 regulates the mutual relationships between the proteins of that family. The proapoptotic effect observed in neutrophils affected by rhIL-17 is a result of a decreased expression of Bcl-xl. Consequently, the expression of apoptogenic proteins, including cytochrome c, Smac/DIABLO, and Omi/HtrA2, is elevated. Surprisingly, there have been no observations of the cytokine influencing the activity of caspase 9. Results have shown for the first time that IL-17 has a direct effect on the decrease of Bcl-xl. In conclusion, the results of the research presented in this article confirm the dual action of IL-17, which, on the one hand, leads to an array of proinflammatory mechanisms regarding neutrophils and, on the other hand, reduces the survival of those cells via an immediate influence on the Bcl-2 family of proteins and apoptogenic factors.