Understanding the Metabolic Profile of Macrophages During the Regenerative Process in Zebrafish

In contrast to mammals, lower vertebrates, including zebrafish (Danio rerio), have the ability to regenerate damaged or lost tissues, such as the caudal fin, which makes them an ideal model for tissue and organ regeneration studies. Since several diseases involve the process of transition between fibrosis and tissue regeneration, it is necessary to attain a better understanding of these processes. It is known that the cells of the immune system, especially macrophages, play essential roles in regeneration by participating in the removal of cellular debris, release of pro- and anti-inflammatory factors, remodeling of components of the extracellular matrix and alteration of oxidative patterns during proliferation and angiogenesis. Immune cells undergo phenotypical and functional alterations throughout the healing process due to growth factors and cytokines that are produced in the tissue microenvironment. However, some aspects of the molecular mechanisms through which macrophages orchestrate the formation and regeneration of the blastema remain unclear. In the present review, we outline how macrophages orchestrate the regenerative process in zebrafish and give special attention to the redox balance in the context of tail regeneration

Cell lipid biology in infections: an overview

Lipids are a big family of molecules with a vast number of functions in the cell membranes, within the cytoplasm, and extracellularly. Lipid droplets (LDs) are the most common storage organelles and are present in almost every tissue type in the body. They also have structural functions serving as building blocks of cellular membranes and may be precursors of other molecules such as hormones, and lipoproteins, and as messengers in signal transduction. Fatty acids (FAs), such as sterol esters and triacylglycerols, are stored in LDs and are used in β-oxidation as fuel for tricarboxylic acid cycle (TCA) and adenosine triphosphate (ATP) generation. FA uptake and entrance in the cytoplasm are mediated by membrane receptors. After a cytoplasmic round of α- and β-oxidation, FAs are guided into the mitochondrial matrix by the L-carnitine shuttle system, where they are fully metabolized, and enter the TCA cycle. Pathogen infections may lead to impaired lipid metabolism, usage of membrane phospholipids, and LD accumulation in the cytoplasm of infected cells. Otherwise, bacterial pathogens may use lipid metabolism as a carbon source, thus altering the reactions and leading to cellular and organelles malfunctioning. This review aims to describe cellular lipid metabolism and alterations that occur upon infections

Lymphocyte Differentiation and Effector Functions

Univ São Paulo, Inst Biomed Sci, Dept Immunol, BR-05508000 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04021001 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04021001 São Paulo, BrazilWeb of Scienc

Editorial: Macrophages role in integrating tissue Signals and Biological Processes in Chronic inflammation and Fibrosis

Univ Sao Paulo, Immunol Dept, Sao Paulo, BrazilINSERM, Paris, FranceUniv Fed Sao Paulo, Nephrol Div, Med Dept, Sao Paulo, BrazilUniv Sao Paulo, Renal Physiol Lab, Fac Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Nephrol Div, Med Dept, Sao Paulo, BrazilWeb of Scienc

The dual effect of acetate on microglial TNF-α production

Introduction: Short-Chain Fatty Acids (SCFA) are products of intestinal microbial metabolism that can reach the brain and alter microglia in health and disease contexts. However, data are conflicting on the effect of acetate, the most abundant SCFA in the blood, in these cells. Objective: The authors aimed to investigate acetate as a modulator of the inflammatory response in microglia stimulated with LPS. Method: The authors used an immortalized cell line, C8-B4, and primary cells for in vitro treatments with acetate and LPS. Cell viability was analyzed by MTT, cytokine by RT-PCR, ELISA, and flow cytometry. The authors also performed in vivo and in silico analyses to study the role of acetate and the TNF-α contribution to the development of Experimental Autoimmune Encephalomyelitis (EAE). Results: Acetate co-administered with LPS was able to exacerbate the production of pro-inflammatory cytokines at gene and protein levels in cell lines and primary culture of microglia. However, the same effects were not observed when acetate was administered alone or as pretreatment, prior to the LPS stimulus. Additionally, pharmacological inhibition of histone deacetylase concomitantly with acetate and LPS led to decreased TNF-α production. In silico analysis showed a crucial role of the TNF-α pathway in EAE development. Moreover, acetate administration in vivo during the initial phase of EAE led to a better disease outcome and reduced TNF-α production. Conclusion: Treatment with acetate was able to promote the production of TNF-α in a concomitant LPS stimulus of microglia. However, the immune modulation of microglia by acetate pretreatment may be a component in the generation of future therapies for neurodegenerative diseases

Activation and Metabolic Shifting: An Essential Process to Mesenchymal Stromal Cells Function

To elucidate the basal metabolism of Mesenchymal Stromal Cells (MSCs), as well as knowing how they are activated, can bring important clues to a successful cell-based therapy. Naive MSCs, in their niche, mainly keep the local homeostasis and the pool of tissue stem cells. Once activated, by an injury, MSCs’ response leads to a lot of physiological differences in its metabolism that are responsible for its healing process. Since endogenous MSC seems to be ineffective in pathologic and aging conditions, cell-based therapy using MSC is focused on administration of exogenous MSC in patients to exert its healing functions. From quiescent to activated state, this “Metabolic Shifting” of MSC interferes directly in its secretion and cellular-derived particle generation. We will address here the differences between the MSCs activation phases and how they can modify the MSCs metabolism and its function. Moreover, understanding MSC in their niche and its damped function in pathologic and aging processes can improve stem cell-based therapies

Intrauterine Undernourishment Alters TH1/TH2 Cytokine Balance and Attenuates Lung Allergic Inflammation in Wistar Rats

IL-4 produced by Th2 cells can block cytokine production by Th1 cells, and Th1 IFN-gamma is known to counterregulate Th2 immune response, inhibiting allergic eosinophilia. As intrauterine undernutrition can attenuate lung inflammation, we investigated the influence of intrauterine undernourishment on the Th1/Th2 cytokine balance and allergic lung inflammation. Intrauterine undernourished offspring were obtained from dams fed 50% of the nourished diet of their counterparts and were immunized at 9 weeks of age. We evaluated the cell counts and cytokine protein expression in the bronchoalveolar lavage, mucus production and collagen deposition, and cytokine gene expression and transcription factors in lung tissue 21 days after ovalbumin immunization. Intrauterine undernourishment significantly reduced inflammatory cell airway infiltration, mucus secretion and collagen deposition, in rats immunized and challenged. Intrauterine undernourished rats also exhibited an altered cytokine expression profile, including higher TNF-alpha and IL-1 beta expression and lower IL-6 expression than well-nourished rats following immunization and challenge. Furthermore, the intrauterine undernourished group showed reduced ratios of the IL-4/IFN-gamma and the transcription factors GATA-3/T-Bet after immunization and challenge. We suggest that the attenuated allergic lung inflammation observed in intrauterine undernourished rats is related to an altered Th1/Th2 cytokine balance resulting from a reduced GATA-3/T-bet ratio. Copyright (C) 2012 S. Karger AG, BaselConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundo de Auxilio aos Docentes e Alunos (FADA-UNIFESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunol Transplantes, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nefrol, Lab Imunol Clin & Expt, BR-09972270 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nefrol, Lab Imunol Clin & Expt, BR-09972270 São Paulo, BrazilFAPESP: 07/07139-3FAPESP: 09/09849-3FAPESP: 09/52119-6FAPESP: 10/01404-0FAPESP: 12/02270-2Web of Scienc

O Aluno com Paralisia Cerebral em Contexto Educativo: Diferenciação de metodologias e estratégias

O modelo de Educação Inclusiva, atualmente implementado e defendido pelas organizações internacionais, pressupõe um único sistema educacional para TODOS os alunos, partindo da aceitação das diferenças individuais e da valorização da diversidade humana, como potenciadores de capacidades num mesmo processo educacional. A Educação Inclusiva não abrange somente crianças/jovens com deficiências, mas alarga a sua intervenção a todos os que, temporária ou permanentemente, apresentem necessidades especiais. Os alunos com Necessidades Educativas Especiais de carácter motor, especialmente Paralisia Cerebral, inseridos no ensino regular, pela especificidade das manifestações apresentadas e das significativas limitações ao nível da atividade e da participação, beneficiarão com a implementação de medidas educativas que diminuam a sua situação de desvantagem e promovam o desenvolvimento das suas potencialidades, recorrendo a metodologias e estratégias facilitadoras do seu desenvolvimento global, que abordaremos numa breve revisão da literatura