RESUMO
Malnutrition is considered one of the most common problems in the elderly population worldwide and can significantly interfere in health evolution in these individuals, predisposing them to increased infection susceptibility. The immune response triggered by infections comprises several mechanisms, and macrophages play important roles in this response. This study aimed to evaluate mechanisms related to macrophage function in a model of protein malnutrition in the elderly. Two age groups (young: 3-5 months and elderly: 18-19 months) male C57BL/6NTac mice were subjected to protein malnutrition with a low-protein diet (2 %). The nutritional status, hemogram and number of peritoneal cells were affected by both age and nutritional status. Additionally, the spreading capacity as well as the phagocytic and fungicidal activity of peritoneal macrophages were affected by the nutritional status and age of the animal. Interestingly, the percentages of F4/80+/CD11b+ and CD86+ cells were reduced mostly in elderly animals, while the TLR-4+ population was more affected by nutritional status than by age. The production of pro-inflammatory cytokines such as TNF-α, IL-1α, and IL-6 was also influenced by nutritional status and/or by age, and malnourished animals of advanced age produced higher amounts of the anti-inflammatory cytokine IL-10. Furthermore, the phosphorylation ratio of the transcription factor NFκB (pNFκB/NFκB) was directly affected by the nutritional status, independently of age. Thus, these results allow us to conclude that aging and protein malnutrition compromise macrophage function, likely affecting their immune function, and in aged protein-malnourished animals, this impairment tends to be more pronounced.
Assuntos
Macrófagos Peritoneais , Desnutrição , Idoso , Humanos , Camundongos , Masculino , Animais , Macrófagos Peritoneais/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: Dietary protein deficiency is common in the elderly, compromising hematopoiesis and the immune response, and may cause a greater susceptibility to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are essential to hematopoiesis. Therefore, this study aimed to investigate, in an aging model subjected to malnutrition due a reduced protein intake, aspects related to the immunomodulatory capacity of MSCs. METHODS: Male C57BL/6 mice from young and elderly groups were fed with normoproteic or hypoproteic diets (12% and 2% of protein, respectively) and nutritional, biochemical and hematological parameters were evaluated. MSCs from bone marrow were isolated, characterized and their secretory parameters evaluated, along with gene expression. Additionally, the effects of aging and protein malnutrition on MSC immunomodulatory properties were assessed. RESULTS: Malnourished mice lost weight and demonstrated anemia, leukopenia, and bone marrow hypoplasia. MSCs from elderly animals from both groups showed reduced CD73 expression and higher senescence rate; also, the malnourished state affected CD73 expression in young animals. The production of IL-1ß and IL-6 by MSCs was affected by aging and malnutrition, but the IL-10 production not. Aging also increased the expression of NFκB, reducing the expression of STAT-3. However, MSCs from malnourished groups, regardless of age, showed decreased TGF-ß and PGE2 production. Evaluation of the immunomodulatory capacity of MSCs revealed that aging and malnutrition affected, mainly in lymphocytes, the production of IFN-γ and IL-10. CONCLUSION: Aging and reduced protein intake are factors that, alone or together, influence the immunomodulatory properties of MSCs and provide basic knowledge that can be further investigated to explore whether MSCs' therapeutic potential may be affected.
Assuntos
Células-Tronco Mesenquimais , Deficiência de Proteína , Envelhecimento , Animais , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Imunidade , Interleucina-10/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Purpose: This study aimed to evaluate the radiation-induced direct and bystander (BYS) responses of mesenchymal stem cells (MSCs) and to characterize these cells radiobiologically.Methods and materials: MSCs were irradiated (IR) and parameters related to DNA damage and cellular signaling were verified in a dose range from 0.5 to 15 Gy; also a transwell insert co-culture system was used to study medium-mediated BYS effects.Results: The main effects on directly IR cells were seen at doses higher than 6 Gy: induction of cell death, cell cycle arrest, upregulation of p21, and alteration of redox status. Irrespective of a specific dose, induction of micronuclei formation, H2AX phosphorylation, and decreased Akt expression also occurred. Thus, mTOR expression, cell senescence, nitric oxide generation, and calcium levels, in general were not significantly modulated by radiation. Data from the linear-quadratic model showed a high alpha/beta ratio, which is consistent with a more exponential survival curve. BYS effects from the unirradiated MSCs placed into companion wells with the directly IR cells, were not observed.Conclusions: The results can be interpreted as a positive outcome, meaning that the radiation damage is restricted to the directed IR MSCs not leading to off-target cell responses.