IL6 inhibition of inflammatory S100A8/9 proteins is NF-κB mediated in essential thrombocythemia.

Autor: Diklić M; Department of Molecular Oncology, Institute for Medical Research, University of Belgrade, Belgade, Serbia., Mitrović-Ajtić O; Department of Molecular Oncology, Institute for Medical Research, University of Belgrade, Belgade, Serbia., Subotički T; Department of Molecular Oncology, Institute for Medical Research, University of Belgrade, Belgade, Serbia., Djikić D; Department of Molecular Oncology, Institute for Medical Research, University of Belgrade, Belgade, Serbia., Kovačić M; Department of Molecular Oncology, Institute for Medical Research, University of Belgrade, Belgade, Serbia., Bjelica S; Department of Molecular Oncology, Institute for Medical Research, University of Belgrade, Belgade, Serbia., Beleslin-Čokić B; Clinic for Endocrinology, Diabetes and Metabolic Diseases, Genetic Laboratory, Clinical Center of Serbia, Belgrade, Serbia., Tošić M; Department of Molecular Oncology, Institute for Medical Research, University of Belgrade, Belgade, Serbia., Leković D; Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.; School of Medicine, University of Belgrade, Belgrade, Serbia., Gotić M; Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.; School of Medicine, University of Belgrade, Belgrade, Serbia., Santibanez JF; Department of Molecular Oncology, Institute for Medical Research, University of Belgrade, Belgade, Serbia., Čokić VP; Department of Molecular Oncology, Institute for Medical Research, University of Belgrade, Belgade, Serbia.
Jazyk: angličtina
Zdroj: Cell biochemistry and function [Cell Biochem Funct] 2020 Jun; Vol. 38 (4), pp. 362-372. Date of Electronic Publication: 2019 Dec 29.
DOI: 10.1002/cbf.3482
Abstrakt: This study has been performed to determine the mechanism of activation of the myeloid related S100A proteins by inflammatory cytokines in myeloproliferative neoplasm (MPN). Besides microarray analysis of MPN-derived CD34 + cells, we analysed the pro-inflammatory IL6 and anti-inflammatory IL10 dependence of NF-κB, PI3K-AKT, and JAK-STAT signalling during induction of S100A proteins in mononuclear cells of MPN, by immunoblotting and flow cytometry. We observed the reduced gene expression linked to NF-κB and inflammation signalling in MPN-derived CD34 + cells. Both IL6 and IL10 reduced S100A8 and 100A9 protein levels mediated via NF-κB and PI3K signalling, respectively, in mononuclear cells of essential thrombocythemia (ET). We also determined the increased percentage of S100A8 and S100A9 positive granulocytes in ET and primary myelofibrosis, upgraded by the JAK2V617F mutant allele burden. S100A8/9 heterodimer induced JAK1/2-dependent mitotic arrest of the ET-derived granulocytes. SIGNIFICANCE OF THE STUDY: We demonstrated that inflammation reduced the myeloid related S100A8/9 proteins by negative feedback mechanism in ET. S100A8/9 can be a diagnostic marker of inflammation in MPN, supported by the concomitant NF-κB and JAK1/2 signalling inhibition in regulation of myeloproliferation and therapy of MPN.
(© 2019 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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