Imatinib treatment inhibit IL-6, IL-8, NF-KB and AP-1 production and modulate intracellular calcium in CML patients

Roberto Ciarcia, Maria Teresa Vitiello, Massimiliano Galdiero, Carmen Pacilio, Valentina Iovane, Danila D'Angelo, David Pagnini, Giuseppe Caparrotti, Daniele Conti, Valentina Tomei, Salvatore Florio, Antonio Giordano

Research output: Contribution to journalArticlepeer-review

Abstract

Imatinib (IM) is considered the gold standard for chronic myeloid leukemia (CML) treatment, although resistance is emerging as a significant problem. The proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) play an important role in cell proliferation, survival, and resistance to glucocorticoid-mediated cell death. Several transcription factors such as NF-KB and AP-1 are activated in response to physiopathological increases and modulation of intracellular calcium levels. Our previous study demonstrated that lymphocytes from CML patients showed dysregulated calcium homeostasis and oxidative stress. Alteration in ionized calcium concentration in the cytosol has been implicated in the initiation of secretion, contraction, and cell proliferation. In this study, we hypothesized that IL-6, IL-8, NF-kB, AP-1, and intracellular calcium may be used as selective and prognostic factors to address the follow-up in CML patients treated with imatinib. Our results demonstrated a significant down-regulation in IL-6 and IL-8 release as well as NF-kB and AP-1 activation in lymphomonocytes from Imatinib-treated patients, compared to samples from untreated patients. In parallel, IM treatment, in vivo and in vitro, were able to modulate the intracellular calcium concentration of peripheral blood mononuclear cells of CML patients by acting at the level of InsP 3 receptor in the endoplasmic reticulum and at the level of the purinergic receptors on plasma membrane. The results of this study show that measurements of NF-kB, AP-1, IL-6, IL-8, and intracellular calcium in CML patients treated with Imatinib may give important information to the hematologist on diagnostic criteria and are highly predictive in patients with newly diagnosed CML.

Original languageEnglish
Pages (from-to)2798-2803
Number of pages6
JournalJournal of Cellular Physiology
Volume227
Issue number6
DOIs
Publication statusPublished - Jun 2012

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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