Dalila Cunha de Oliveira

The effects of protein malnutrition on the TNF-RI and NF-κB expression via the TNF-α signaling pathway

Malnutrition is a nutritional condition that can affect many aspects of the immunological response, including by decreasing cell migration and stimulating phagocytosis; the bactericidal response; changes in reactive oxygen and nitrogen species production; and the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α). This cytokine is primarily produced by macrophages and is associated with a wide range of biological activities, including inflammatory processes, growth, differentiation, and apoptosis. TNF-α acts through the activation of TNF receptors, and mainly receptor I (TNF-RI), which is responsible for most of the effects of TNF-α. This activation triggers a series of intracellular events that result in the activation of the transcription factor NF-κB. In this study, we evaluated the expression of the transcription factor NF-κB, mediated by TNF-α through TNF-RI, in a protein malnutrition (PM) model. Adult male BALB/c mice were submitted to PM, and after loss of approximately 20% of their body weight, their peritoneal macrophages were collected and cultivated with or without TNF-α. The expression of TNF-RI and proteins in its signaling pathway (TRADD, TRAF, RIP, IKK, IKB-α, pIKB-α, NF-κB, and pNF-κB) were evaluated, as well as cytokine production (IL-1α, IL-1β, IL-6, and IL-12). The compiled results highlight that the malnourished animals presented anemia, leukopenia, and decreased peritoneal cellularity. TNF-RI expression was reduced in the malnourished animals, and NF-κB phosphorylation was also reduced, in association with reduced production of IL-1β and IL-12. In this study, we observed aspects related to the innate immune response, and the outcome data allowed us to conclude that nutritional status interferes with the macrophage activation and the response capabilities of these cells.

Protein Malnutrition Alters Spleen Cell Proliferation and IL-2 and IL-10 Production by Affecting the STAT-1 and STAT-3 Balance

Protein malnutrition (PM) is an important public health problem that affects resistance to infection by impairing a number of physiological processes. PM induces structural changes in the lymphoid organs that affect the roles of the immune and inflammatory responses in a crucial way. The activation of different transcription factors, including signal transducer and activator of transcription (STAT) family members, leads to the production of different cytokines, which are mediators essential to mounting adequate immune and inflammatory responses. In this study, malnourished animals presented anemia, leukopenia, and a severe reduction in spleen cellularity, with reduced numbers of most cell populations, as well as increased percentages of CD3+ and CD4+ cells. The proliferation rates were reduced, and cells were increasingly observed in the G0/G1 cell cycle phase; further, IL-2 production was reduced, while IL-10 production was increased. In spleen cells from malnourished animals, STAT-3 protein expression was increased, with a concomitant reduction in STAT-1 expression. Knowing that STAT-1 and STAT-3 are key transcription factors in both immunity and inflammatory pathways, these results infer, at least in part, a mechanistic pathway that affects the manner or intensity of the immune response in malnourished individuals, increasing susceptibility to infection.

Glutamine metabolism and its effects on immune response: molecular mechanism and gene expression

This article aims to review glutamine metabolism and its effects on the immune response. Selected topics are addressed, particularly the effect of glutamine on cell survival and proliferation, as well as its importance in some biochemical pathways. The impact of glutamine on muscle, intestine, and liver metabolism are described, and a special section about glutamine regulation of the immune response is included. In this context, the modulation of glutamine on relevant signaling pathways as nuclear factor kappa B (NF-kB), mitogen-activated protein kinases (MAPKs), and heat shock protein and the influence of this amino acid on cell migration and adhesion molecules are highlighted. Some important immune response pathways modulated by glutamine were described as its action in critically ill patients. In summary, this review describes some important actions of glutamine, and a range of reactions and modulatory effects in different organs, which may inform new therapeutic strategies. However, further studies are necessary to provide information about glutamine use, especially about situations in which it can be better used as well as fine-tuning dose and administration.

High-fat diet or low-protein diet changes peritoneal macrophages function in mice

BackgroundObesity and protein malnutrition are major food problems nowadays, affecting billions of people around the world. The nutrition transition that has occurred in recent decades is changing the nutritional profile, reducing malnutrition and increasing the percentage of obese people. The innate immune response is greatly influenced by diet, with significant changes in both malnutrition and obesity. Therefore, we investigate the effects of protein malnutrition and obesity in nutritional and immunological parameters in mice.ResultsPeritoneal macrophages of malnourished animals showed reduced functions of adhesion, spreading, and fungicidal activity; production of hydrogen peroxide and nitric oxide were lower, reflecting changes in the innate immune response. However, the high-fat animals had macrophage functions slightly increased.ConclusionsAnimals subjected to low-protein diet have immunosuppression, and animals subjected to high-fat diet increased visceral adipose tissue and the presence of an inflammatory process with increased peritoneal macrophage activity and similar systemic changes to metabolic syndrome.

Hematological alterations in protein malnutrition

Protein malnutrition is one of the most serious nutritional problems worldwide, affecting 794 million people and costing up to

Effects of short-term dietary restriction and glutamine supplementation in vitro on the modulation of inflammatory properties

3.5 trillion annually in the global economy. Protein malnutrition primarily affects children, the elderly, and hospitalized patients. Different degrees of protein deficiency lead to a broad spectrum of signs and symptoms of protein malnutrition, especially in organs in which the hematopoietic system is characterized by a high rate of protein turnover and, consequently, a high rate of protein renewal and cellular proliferation. Here, the current scientific information about protein malnutrition and its effects on the hematopoietic process is reviewed. The production of hematopoietic cells is described, with special attention given to the hematopoietic microenvironment and the development of stem cells. Advances in the study of hematopoiesis in protein malnutrition are also summarized. Studies of protein malnutrition in vitro, in animal models, and in humans demonstrate several alterations that impair hematopoiesis, such as structural changes in the extracellular matrix, the hematopoietic stem cell niche, the spleen, the thymus, and bone marrow stromal cells; changes in mesenchymal and hematopoietic stem cells; increased autophagy; G0/G1 cell-cycle arrest of progenitor hematopoietic cells; and functional alterations in leukocytes. Structural and cellular changes of the hematopoietic microenvironment in protein malnutrition contribute to bone marrow atrophy and nonestablishment of hematopoietic stem cells, resulting in impaired homeostasis and an impaired immune response.

Valores de referência hematológicos e bioquímicos para camundongos das linhagens C57BL/6, Swiss Webster e BALB/c

OBJECTIVE Dietary restriction (DR) is a nutritional intervention that exerts profound effects on biochemical and immunologic parameters, modulating some inflammatory properties. Glutamine (GLN) is a conditionally essential amino acid that can modulate inflammatory properties. However, there is a lack of data evaluating the effects of DR and GLN supplementation, especially in relation to inflammatory cytokine production and the expression of transcription factors such as nuclear factor (NF)-κB. METHODS We subjected 3-mo-old male Balb/c mice to DR by reducing their food intake by 30%. DR animals lost weight and showed reduced levels of serum triacylglycerols, glucose, cholesterol, and calcium as well as a reduction in bone density. Additionally, blood, peritoneal, and spleen cellularity were reduced, lowering the number of peritoneal F4/80- and CD86-positive cells and the total number of splenic CD4- and CD8-positive cells. RESULTS The production of interleukin (IL)-10 and the expression of NF-κB in splenic cells were not affected by DR or by GLN supplementation. However, peritoneal macrophages from DR animals showed reduced IL-12 and tumor necrosis factor-α production and increased IL-10 production with reduced phosphorylation of NF-κB expression. Additionally, GLN was able to modulate cytokine production by peritoneal cells from the control group, although no effects were observed in cells from the DR group. CONCLUSION DR induces biochemical and immunologic changes, in particular by reducing IL-12 and tumor necrosis factor-α production by macrophages and clearly upregulating IL-10 production, whereas GLN supplementation did not modify these parameters in cells from DR animals.