Aneuploidy assessed by DNA index influences the effect of iron status on plasma and/or supernatant cytokine levels and progression of cells through the cell cycle in a mouse model |
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| Institution: | 1. Louisiana State University Health Sciences Center, Department of Pediatrics, The Research Institute for Children’s Hospital, USA;2. Department of Pulmonary Medicine,1542 Tulane Avenue, New Orleans, LA 70112, USA;3. University of South Alabama College of Medicine, Department of Pediatrics, 2451 Fillingim St., Mobile, AL 36617, USA;1. Department of Dermatology, Tokyo Medical University, Tokyo, Japan;2. Department of Dermatology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan;3. Department of Oncology, Roswell Park Cancer Center, New York, USA;1. Department of Surgery, Loyola University Chicago, Stritch School of Medicine, United States;2. Department of Molecular Pharmacology & Therapeutics, Loyola University Chicago, Stritch School of Medicine, United States;3. Department of Biochemistry, Medical College of Wisconsin, United States;1. College of Veterinary Medicine, Sichuan Agricultural University, Sichuan Province Key Laboratory of Animal Disease & Human Health, Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya’an, 625014, China;2. School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, 621010, China;1. Department of Pathology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA;2. Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang 110001, China;3. Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA;4. Department of Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA;1. Database/Bioinformatics Laboratory, Chungbuk National University, Cheongju, Korea;2. Division of Bio-Medical Informatics, Center for Genome Science, Korea National Institute of Health, Cheongju, Korea |
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| Abstract: | Aneuploidy, a condition associated with altered chromosome number, hence DNA index, is frequently seen in many diseases including cancers and affects immunity. Iron, an essential nutrient for humans, modulates the immune function and the proliferation of normal and cancer cells. To determine whether impaired immunity seen in iron-deficient subjects may be related to aneuploidy, we measured spleen cell DNA index, percent of cells in different phases of the cell cycle, plasma and/or supernatant IL-2, IL-10, IL-12, and interferon-gamma in control, pair-fed, iron-deficient, and iron-replete mice (N = 20–22/group). The test and control diets differed only in iron content (0.09 mmol/kg versus 0.9 mmol/kg) and were fed for 68 days. Mean levels of hemoglobin and liver iron stores of iron-deficient and iron-replete mice were 40–60% lower than those of control and pair-fed mice (P < 0.05). Mean plasma levels of IL-10, interferon-gamma and percent of cells in S + G2/M phases were lower in mice with than in those without aneuploidy (P < 0.05). Lowest plasma IL-12 and interferon-gamma concentrations were observed in iron-deficient mice with aneuploidy. Mean percents of cultures with aneuploidy and DNA indexes were higher in iron-deficient and iron-replete than in control and pair-fed mice likely due to delayed cell division (P < 0.05). Aneuploidy decreased the concentration of IL-2 and interferon-gamma in baseline cultures while it increased that of interferon-gamma in anti-CD3 treated cultures. Aneuploidic indexes negatively correlated with cytokine levels, percents of cells in S + G2/M phases and indicators of iron status (P < 0.05). Although chromosome cytogenetics was not performed, for the first time, we report that increased aneuploidy rate may modulate the immune function during iron-deficiency. |
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| Keywords: | Iron deficiency Aneuploidy Lymphocyte proliferation Cytokines Mitogens |
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