The influence of protein malnutrition on biological and immunomodulatory aspects of bone marrow mesenchymal stem cells.
Tissues that require a great supply of nutrients and possess high metabolic demands, such as lympho-hemopoietics tissues, are the first to be affected by protein malnutrition (PM). Thus, PM directly affects hemopoiesis and the production and function of immune cells. Consequently, malnourished individuals are more susceptible to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are important in the formation of lympho-hemopoietic stroma. Since an adequate supply of nutrients is essential to sustain stroma formation, which is mainly constituted of MSCs and differentiated cells originated from them, this study investigated whether PM would influence some biological and immunomodulatory aspects of MSCs. Two-month-old Balb/c mice were divided into control and malnourished groups receiving normoproteic or hypoproteic diets, respectively (12% and 2% of protein) for 28 days. MSCs obtained from control (MSCct) and malnourished (MSCmaln) animals were characterized. In addition, the proliferation rate and cell cycle protein expression were determined, but no differences in these parameters were observed. In order to evaluate whether PM affects the immunomodulatory properties of MSCs, the expression of NFκB and STAT-3, and the production of IL-1α, IL-1β, IL-6, IL-10, TGF-β and TNF-α by MSCs were assessed. MSCmaln expressed lower levels of NF-κB and the production of IL-1β, IL-6 and TGF-β was significantly influenced by PM. Furthermore, MSCct and MSCmaln culture supernatants affected lymphocyte and macrophage proliferation. However, MSCmaln did not reduce the production of IFN-γ nor stimulate the production of IL-10 in lymphocytes in the same manner as observed in MSCct. Overall, this study implied that PM modifies immunosuppressive properties of MSCs.
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-900 São Paulo, SP, Brazil.
Guilherme Galvão
GG
Dos Santos
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-900 São Paulo, SP, Brazil; Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology(NUST), H-12, Islamabad, Pakistan.
Shafqat
S
Batool
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-900 São Paulo, SP, Brazil.
Araceli
A
Hastreiter
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-900 São Paulo, SP, Brazil.
Talita
T
Sartori
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-900 São Paulo, SP, Brazil.
Amanda
A
Nogueira-Pedro
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-900 São Paulo, SP, Brazil.
Primavera
P
Borelli
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-900 São Paulo, SP, Brazil. Electronic address: hemato@usp.br.
Ricardo Ambrosio
RA
Fock
D056704:Adaptive Immunity; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004044:Dietary Proteins; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D056747:Immunomodulation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008807:Mice, Inbred BALB C; D011488:Protein Deficiency / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D011502:Protein-Energy Malnutrition / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D017077:Culture Media, Conditioned; D016207:Cytokines; D004044:Dietary Proteins
Cell cycle; Cytokines; Immunomodulation; Mesenchymal stem cells; Protein malnutrition