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Evaluating the mechanism underlying antitumor effect of interleukin 27 on B cells of chronic lymphocytic leukemia patients.

Abstract
Chronic lymphocyte leukemia (CLL) is a B-cell malignancy resisted to apoptosis. Recently, some studies indicated that cytokines such as interleukin 27 (IL-27) can reduce B-cell proliferation. The aim of this study is to evaluate the mechanism underlying the proapoptotic effect of IL-27 on B cells of patients with CLL in comparison with B cells of normal subjects. The effect of IL-27 on the antitumor activity of natural killer (NK) and T cells was also evaluated. Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with CLL and 15 normal subjects. B cells and PBMCs were cocultured with IL-27 and B cells apoptosis to evaluate proliferation. Both messenger RNA and protein expression of IL-27 and IL-27 receptor were determined using flow cytometry and real-time polymerase chain reaction analysis. To evaluate the apoptotic effect of IL-27 on B cells of patients with CLL, Annexin V-FITC and 7-AAD (BioLegend) fluorescent dyes were used. In addition, the IL-27 effect on activation of T cell and NK cell was determined by determining CD96 molecule expression. IL-27 and IL-27 receptor expression in patients with CLL was significantly lower than that of normal subjects (p < .05). IL-27 enhanced apoptosis of B cells in patients with CLL (p < .05) but this effect was not significantly observed in B cells of normal subjects (p > .05). Consequently, IL-27 reduced the proliferation of B cells and enhanced NK cell activity (p < .05). IL-27, through inducing apoptosis, can exert an inhibitory effect on cancer B cells of CLL patients with minimal effect on normal B cells.
AuthorsEhsan Manouchehri-Doulabi, Somaye Abbaspour, Shahrbano Rostami, Mohammad Faranoush, Farahnaz Ghahramanfard, Fatemeh Pak, Mehdi Barati, Parviz Kokhaei, Amir A Momtazi-Borojeni
JournalJournal of cellular physiology (J Cell Physiol) Vol. 235 Issue 12 Pg. 9424-9431 (12 2020) ISSN: 1097-4652 [Electronic] United States
PMID32383245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2020 Wiley Periodicals LLC.
Chemical References
  • Interleukins
  • MYDGF protein, human
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis (drug effects)
  • B-Lymphocytes (drug effects, pathology)
  • Cell Proliferation (drug effects)
  • Female
  • Humans
  • Interleukins (metabolism, pharmacology)
  • Killer Cells, Natural (immunology)
  • Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, metabolism)
  • Leukocytes, Mononuclear (drug effects, metabolism)
  • Lymphocyte Activation (drug effects)
  • Male
  • Middle Aged
  • T-Lymphocytes (drug effects)

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