TNF-alpha regulates the effects of irradiation in the mouse bone marrow microenvironment.

PloS One
Ana Sofia CachaçoSérgio Dias

Abstract

Secondary bone marrow (BM) myelodysplastic syndromes (MDS) are increasingly common, as a result of radio or chemotherapy administered to a majority of cancer patients. Patients with secondary MDS have increased BM cell apoptosis, which results in BM dysfunction (cytopenias), and an increased risk of developing fatal acute leukemias. In the present study we asked whether TNF-alpha, known to regulate cell apoptosis, could modulate the onset of secondary MDS. We show that TNF-alpha is induced by irradiation and regulates BM cells apoptosis in vitro and in vivo. In contrast to irradiated wild type (WT) mice, TNF-alpha deficient (TNF-alpha KO) mice or WT mice treated with a TNF-alpha-neutralizing antibody were partially protected from the apoptotic effects of irradiation. Next we established a 3-cycle irradiation protocol, in which mice were sub-lethally irradiated once monthly over a 3 month period. In this model, irradiated WT mice presented loss of microsatellite markers on BM cells, low white blood cell (WBC) counts, reduced megakaryocyte (MK) and platelet levels (thrombocytopenia) and macrocytic anemia, phenoypes that suggest the irradiation protocol resulted in BM dysfunction with clinical features of MDS. In contrast, TNF-alp...Continue Reading

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Citations

May 28, 2013·TheScientificWorldJournal·Ning ZhangHang Li
Jan 27, 2012·Radiation and Environmental Biophysics·Jiřina VávrováEmilie Lukášová
Oct 14, 2014·The Prostate·Natalie A VenierVasundara Venkateswaran
Nov 10, 2013·Blood·Juan I Garaycoechea, K J Patel
Jan 2, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rama MalaviyaDebra L Laskin
Dec 22, 2016·Nature Communications·Michael G PoulosJason M Butler
Jan 22, 2015·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·H XiongZ L Zou
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Jan 22, 2011·Current Opinion in Hematology·Ravi Bhatia, H Joachim Deeg
Nov 20, 2015·Journal of Orthopaedic Trauma·Peter V GiannoudisChelsea Bahney
Sep 25, 2019·Archives of Pharmacal Research·Xinyan QuZhe Zhou
Nov 24, 2020·Cancer Investigation·Hassan RafieemehrNajmaldin Saki
May 1, 2021·Cancers·Ekaterina O GubernatorovaSergei A Nedospasov

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Methods Mentioned

BETA
MDS
ELISA
flow cytometry
enzyme-linked immunosorbent assay
fluorescence microscopy

Software Mentioned

Image J
âCell Questâ

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