ABSTRACT
BACKGROUND: IL-17, classified as an inflammatory cytokine, plays a key role in the activation of inflammatory processes involving neutrophils. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Interleukin-17/blood , Mitochondria/metabolism , Neutrophils/metabolism , bcl-X Protein/blood , Adult , Apoptosis , Apoptosis Regulatory Proteins , Blood Donors , Cell Survival , Cytochromes c/blood , Granulocytes/metabolism , Healthy Volunteers , High-Temperature Requirement A Serine Peptidase 2 , Humans , Inflammation , Intracellular Signaling Peptides and Proteins/blood , Middle Aged , Mitochondrial Proteins/blood , N-Formylmethionine Leucyl-Phenylalanine/metabolism , Serine Endopeptidases/blood , Young AdultABSTRACT
PURPOSE: The purpose of the study was the assessment of the expression of IL-1ß and IL-6, and the proteins regulating their biological activity, namely IL-1RII, IL-1Ra, as well as sIL-6Rα, sgp-130 in leukemic lymphocytes and autologous neutrophils of B-CLL patients. MATERIAL/METHODS: The study involved a group of B-cell chronic lymphocytic leukemia patients and healthy volunteer blood donors. The presence of chosen proteins and their natural regulators was confirmed by Western blot. RESULTS: Western blot analysis showed a decreased expression of IL-1ß and IL-6 in the leukocytes of B-CLL patients. Decreased expression of sIL-6Rα has been observed in lymphocytes, with a simultaneous increase of expression in PMNs. Lower expression of sgp-130 was found in B cells while its expression was elevated in the neutrophils of patients in early stages of the disease. CONCLUSIONS: The changes observed in the expression of IL-1 and IL-6 seem to exclude their immediate involvement in the progress of B-CLL. However, the presented changes in the expression of proteins regulating IL-1ß and IL-6 in PMNs indicate a potential role of early immune response cells also in advanced stages of the disease.