Área de PDI em Pesquisa, Desenvolvimento e Inovação em Mecanismos Imunológicos e Estratégias de Imunoproteção 2013
Veja, abaixo, a relação de artigos científicos publicados pelo IOC, na referida Área Temática, organizados em ordem alfabética crescente:
| Alberto AVP, Faria RX, Couto CGC, Ferreira LGB, Souza CAM, Teixeira PCN, Fróes MM and Alves LA (2013), "Is pannexin the pore associated with the P2X7 receptor?", Naunyn Schmiedebergs Arch Pharmacol., Sep, 2013. Vol. 386(9), pp. 775-787. [DOI] |
| Abstract: The P2X7 receptor (P2X7R), an ATP-gated cation channel, is expressed predominantly in leukocytes. Activation of P2X7R has been implicated in the formation of a cytolytic pore (i.e., a large conductance channel) that allows the passage of molecules up to 900 Da in macrophages. At least two hypotheses have been presented to explain the conversion of a nonselective cation channel to a cytolytic pore. One hypothesis suggests that the pore is a separate molecular structure activated by P2X7R, and the second asserts that this is an intrinsic property of P2X7R (pore dilation). Based on connexin knockout and hemichannel antagonist studies, some groups have concluded that connexins and pannexins, the hemichannel-forming proteins in vertebrates, are fundamental components of the large conductance channel associated with P2X7R. Dye uptake and electrophysiology experiments were used to evaluate the efficacy and specificity of some hemichannel antagonists under conditions known to open the large conductance channel associated with P2X7R. Hemichannel antagonists and interference RNA (RNAi) targeting pannexin-1 did not affect P2X7R macroscopic currents [ATP, 1,570±189 pA; ATP+100 μM carbenoxolone (CBX), 1,498±100 pA; ATP+1 mM probenecid (Prob), 1,522±9 pA] or dye uptake in a FACS assay (ATP, 63±5 ATP+100 μM CBX, 51.51±8.4 ATP+1 mM Prob, 57.7±4.3 in mouse macrophages. These findings strongly suggest that the high-permeability pore evident after prolonged P2X7R activation does not occur through connexin or pannexin hemichannels in murine macrophages. Another membrane protein may be involved in P2X7R pore formation. |
BibTeX: @article{Alberto2013, author = {Alberto, A V P. and Faria, R. X. and Couto, C G C. and Ferreira, L G B. and Souza, C A M. and Teixeira, P C N. and Fróes, M. M. and Alves, L. A.}, title = {Is pannexin the pore associated with the P2X7 receptor?}, journal = {Naunyn Schmiedebergs Arch Pharmacol}, year = {2013}, volume = {386}, number = {9}, pages = {775--787}, url = {http://dx.doi.org/10.1007/s00210-013-0868-x}, doi = {10.1007/s00210-013-0868-x} } |
| Alves LA, Bezerra RJS, Faria RX, Ferreira LGB and da Silva Frutuoso V (2013), "Physiological roles and potential therapeutic applications of the P2X7 receptor in inflammation and pain.", Molecules. Vol. 18(9), pp. 10953-10972. [DOI] |
| Abstract: The P2X7 receptor (P2X7R) is a nonselective cation channel that is activated by extracellular ATP and triggers the secretion of several proinflammatory substances, such as IL-1β, IL-18, TNF-α, and nitric oxide. Recently, several preclinical studies have demonstrated that this receptor participates in inflammation and pain mechanisms. Taken together, these results indicate that P2X7R is a promising pharmacological target, and compounds that modulate the function of this receptor show potential as new anti-inflammatory medicines. In this review, we discuss aspects of P2X7R pharmacology and the participation of this protein in inflammation and pain and provide an overview of some promising compounds that have been tested as antagonists of P2X7R, with clinical applicability. |
BibTeX: @article{Alves2013, author = {Alves, Luiz Anastacio and Bezerra, Rômulo José Soares and Faria, Robson Xavier and Ferreira, Leonardo Gomes Braga and da Silva Frutuoso, Valber}, title = {Physiological roles and potential therapeutic applications of the P2X7 receptor in inflammation and pain.}, journal = {Molecules}, year = {2013}, volume = {18}, number = {9}, pages = {10953--10972}, url = {http://dx.doi.org/10.3390/molecules180910953}, doi = {10.3390/molecules180910953} } |
| Da Silva SV, Salama C, Renovato-Martins M, Helal-Neto E, Citelli M, Savino W and Barja-Fidalgo C (2013), "Increased Leptin Response and Inhibition of Apoptosis in Thymocytes of Young Rats Offspring from Protein Deprived Dams during Lactation", Plos One., May, 2013. Vol. 8(5), pp. e64220. Public Library Science. [DOI] |
| Abstract: We investigated the consequences of mild maternal malnutrition in rat dams, in terms of thymocyte responses and the putative role of leptin. The young progeny of dams submitted to protein deprivation (PD) during lactation showed at 30 days of age lower body and thymus weights, significant alterations in CD4/CD8-defined T cell subsets without modifications in total thymocyte number as well as in proliferative response. Despite, the rats from PD group did not present alterations in leptin circulating levels, the expression of leptin receptor ObRb was enhanced in their thymocytes. This change was accompanied by an increase in leptin signaling response of thymocytes from PD rats, with an increase in JAK2 and STAT3 phosphorylation after leptin stimulation. Thymocytes from PD rats also presented a decreased rate of spontaneous apoptosis when compared to controls. Accordingly, higher expression of anti-apoptotic protein Bcl-2, and lower of pro-apoptotic protein Bax, with no change of pro-apoptotic Bad, and higher pro-caspase 3 content were detected in PD thymocytes. Moreover, thymocytes from PD group exhibited a constitutive higher nuclear content of p65 NF-kB associated to a lower IkB content in the cytoplasm. Finally, although there was no change in ob gene expression in PD thymocytes, a higher mRNA expression for the Ob gene was observed in the thymic microenvironment from PD animals. Taken together, the results show that mild maternal protein deprivation during lactation affects thymic homeostasis, enhancing leptin activity, which in turn protects thymocytes from apoptosis in the young progeny, with possible consequences upon the immune response of these animals in adult life. |
BibTeX: @article{Silva2013a, author = {Da Silva, S. V. and Salama, C. and Renovato-Martins, M. and Helal-Neto, E. and Citelli, M. and Savino, W. and Barja-Fidalgo, C.}, title = {Increased Leptin Response and Inhibition of Apoptosis in Thymocytes of Young Rats Offspring from Protein Deprived Dams during Lactation}, journal = {Plos One}, publisher = {Public Library Science}, year = {2013}, volume = {8}, number = {5}, pages = {e64220}, doi = {10.1371/journal.pone.0064220} } |
| De Meis J and Savino W (), "Mature peripheral T cells are important to preserve thymus function and selection of thymocytes during Mycobacterium tuberculosis infection", Immunotherapy. [DOI] |
| Abstract: Evaluation of: Nobrega C, Nunes-Alves C, Cerqueira-Rodrigues B et al. T cells home to the thymus and control infection. J. Immunol. 190, 1646-1658 (2013). It is well documented that the thymus is a target organ for a large variety of pathogens (virus, bacteria, fungi and protozoa). Moreover, the presence of pathogen-derived antigens in the thymus of infected mice seems to interfere with the capacity of mature T cells to respond to the invading organism. In this way, Nobrega and colleagues demonstrated in 2010 that Mycobacterium avium infection in the thymus leads to the appearance of differentiated T cells tolerogenic for bacterial antigens. In the present and elegant study, the same group demonstrates that T-cell recirculation from the periphery to the thymus is a mechanism that allows the immune system to respond to thymic infection. A Mycobacterium-infected thymus increases the production of Th1-effector chemokines, such as CXCL9 and CXCL10, which in turn recruit CXCR3(+) peripheral T cells involved in intrathymic bacterial control. Taken together, these findings may represent an important issue of the host response, in terms of different pathogens able to infect the thymus. |
BibTeX: @article{Meis, author = {De Meis, J. and Savino, W.}, title = {Mature peripheral T cells are important to preserve thymus function and selection of thymocytes during Mycobacterium tuberculosis infection}, journal = {Immunotherapy}, doi = {10.2217/imt.13.41} } |
| Ferreira-Machado SC, Salata C, Rocha NN, Correa AFS, Corte-Real S, Peregrino AAF, De Campos VMA, Andrade CBV, Bernardo M, Cabral-Neto JB and Dealmeida CE (2013), "Caspase-3 activation and increased procollagen type I in irradiated hearts", Anais Da Academia Brasileira De Ciencias., March, 2013. Vol. 85(1), pp. 215-222. Acad Brasileira De Ciencias. [DOI] |
| Abstract: The caspase-3-cleaved presence was evaluated in this study in the heart of irradiated rats, during the decline of ventricular function. Female Wistar rats were irradiated with a single dose of radiation (15 Gy) delivered directly to the heart and the molecular, histological and physiological evaluations were performed at thirteen months post-irradiation. The expressions of procollagen type I, TGF-beta 1 and caspase-3-cleaved were analyzed using Western blotting. Cardiac structural and functional alterations were investigated by echocardiography and electron microscopy. In the irradiated group, the levels of procollagen type I, TGF-beta 1 and caspase-3-cleaved are increased. Significant histological changes (degeneration of heart tissue and collagen deposition) and functional (reduced ejection fraction) were observed. Data suggest that the cardiac function decline after exposure to ionizing radiation is related, in part, to increased collagen and increased caspase-3-cleaved. |
BibTeX: @article{Ferreira-Machado2013, author = {Ferreira-Machado, S. C. and Salata, C. and Rocha, N. N. and Correa, A. F. S. and Corte-Real, S. and Peregrino, A. A. F. and De Campos, V. M. A. and Andrade, C. B. V. and Bernardo, M. and Cabral-Neto, J. B. and Dealmeida, C. E.}, title = {Caspase-3 activation and increased procollagen type I in irradiated hearts}, journal = {Anais Da Academia Brasileira De Ciencias}, publisher = {Acad Brasileira De Ciencias}, year = {2013}, volume = {85}, number = {1}, pages = {215--222}, doi = {10.1590/S0001-37652013005000009} } |
| Mietto BS, Jurgensen S, Alves L, Pecli C, Narciso MS, Assuncao-Miranda I, Villa-Verde DMS, Lima FRD, de Menezes JRL, Benjamim CF, Bozza MT and Martinez AMB (), "Lack of galectin-3 speeds Wallerian degeneration by altering TLR and pro-inflammatory cytokine expressions in injured sciatic nerve", European Journal of Neuroscience. [DOI] |
| Abstract: Wallerian degeneration (WD) comprises a series of events that includes activation of non-neuronal cells and recruitment of immune cells, creating an inflammatory milieu that leads to extensive nerve fragmentation and subsequent clearance of the myelin debris, both of which are necessary prerequisites for effective nerve regeneration. Previously, we documented accelerated axon regeneration in animals lacking galectin-3 (Gal-3), a molecule associated with myelin clearance. To clarify the mechanisms underlying this enhanced regeneration, we focus here on the early steps of WD following sciatic nerve crush in Gal-3/ mice. Using an in vivo model of nerve degeneration, we observed that removal of myelin debris is more efficient in Gal-3/ than in wild-type (WT) mice; we next used an in vitro phagocytosis assay to document that the phagocytic potential of macrophages and Schwann cells was enhanced in the Gal-3/ mice. Moreover, both RNA and protein levels for the pro-inflammatory cytokines IL-1 and TNF-, as well as for Toll-like receptor (TLR)-2 and -4, show robust increases in injured nerves from Gal-3/mice compared to those from WT mice. Collectively, these data indicate that the lack of Gal-3 results in an augmented inflammatory profile that involves the TLRcytokine pathway, and increases the phagocytic capacity of Schwann cells and macrophages, which ultimately contributes to speeding the course of WD. |
BibTeX: @article{Mietto, author = {Mietto, B. S. and Jurgensen, S. and Alves, L. and Pecli, C. and Narciso, M. S. and Assuncao-Miranda, I. and Villa-Verde, D. M. S. and Lima, F. R. D. and de Menezes, J. R. L. and Benjamim, C. F. and Bozza, M. T. and Martinez, A. M. B.}, title = {Lack of galectin-3 speeds Wallerian degeneration by altering TLR and pro-inflammatory cytokine expressions in injured sciatic nerve}, journal = {European Journal of Neuroscience}, doi = {10.1111/ejn.12161} } |
| Pacheco PAF, Ferreira LGB, Alves LA and Faria RX (2013), "Modulation of P2 receptors on pancreatic β-cells by agonists and antagonists: a molecular target for type 2 diabetes treatment.", Curr Diabetes Rev., May, 2013. Vol. 9(3), pp. 228-236. [DOI] |
| Abstract: Morbidity and mortality from diabetes mellitus (DM) are serious worldwide concerns. By the year 2030, the estimated number of diabetic patients will reach a staggering 439 million worldwide. Diabetes mellitus type 2 (DM2), which involves disturbances in both insulin secretion and resistance, is the most common form of diabetes and affects approximately 5 to 7% of the world's population. When a patient with DM2 cannot regulate his or her blood glucose levels through diet, weight loss, or exercise, oral medications, such as hypoglycemic agents (i.e., sulphonylureas, biguanides, alpha glucosidase inhibitors and thiazolidinediones), are crucial. Here, we discuss some physiological aspects of P2 receptors on pancreatic β-cells, which express a variety of P2 receptor isoforms. These receptors enhance glucose-dependent insulin release. In addition, we speculate on the potential of purinergic compounds as novel or additional treatments for Type 2 Diabetes mellitus. |
BibTeX: @article{Pacheco2013, author = {Pacheco, Paulo Anastácio Furtado and Ferreira, Leonardo Gomes Braga and Alves, Luiz Anastacio and Faria, Robson Xavier}, title = {Modulation of P2 receptors on pancreatic β-cells by agonists and antagonists: a molecular target for type 2 diabetes treatment.}, journal = {Curr Diabetes Rev}, year = {2013}, volume = {9}, number = {3}, pages = {228--236}, doi = {10.2174/1573399811309030004} } |
| Perone MJ, Velazquez G, De Arias AR, Chamorro G, Coluchi N, Pirmez C, Savino W, Barbeito L and Arzt E (2013), "First South American Network of Biomedical Research. Education and Biotechnology for Health", Medicina-buenos Aires. Vol. 73(1), pp. 75-77. Medicina (buenos Aires). |
| Abstract: First South American Network of Biomedical Research. Education and Biotechnology for Health. It is in our interest, in this brief manuscript, to report the creation of the first program of regional integration of a network of research institutes in Biomedicine belonging to members of the MERCOSUR countries. We discuss some of the foundations that gave sustenance to its creation and its objectives in the medium and long term. In addition, we consider the potential of the results of this program in the fields of applied medical research, education and biotechnology. |
BibTeX: @article{Perone2013, author = {Perone, M. J. and Velazquez, G. and De Arias, A. R. and Chamorro, G. and Coluchi, N. and Pirmez, C. and Savino, W. and Barbeito, L. and Arzt, E.}, title = {First South American Network of Biomedical Research. Education and Biotechnology for Health}, journal = {Medicina-buenos Aires}, publisher = {Medicina (buenos Aires)}, year = {2013}, volume = {73}, number = {1}, pages = {75--77} } |
| Ponte CGG, Antas PRZ, Peres LM and Marinho SP (2013), "Comments on the Neonatal Bacillus Calmette-Guerin Vaccination: Adding Notes in Proof of Nonspecific Effect", American Journal of Respiratory and Critical Care Medicine., April, 2013. Vol. 187(7), pp. 778-779. Amer Thoracic Soc. [DOI] |
BibTeX: @article{Ponte2013, author = {Ponte, C. G. G. and Antas, P. R. Z. and Peres, L. M. and Marinho, S. P.}, title = {Comments on the Neonatal Bacillus Calmette-Guerin Vaccination: Adding Notes in Proof of Nonspecific Effect}, journal = {American Journal of Respiratory and Critical Care Medicine}, publisher = {Amer Thoracic Soc}, year = {2013}, volume = {187}, number = {7}, pages = {778--779}, doi = {10.1164/ajrccm.187.7.778} } |
| Silva JL, Souza MC, Ferreira-DaSilva CT, Silva LS, Costa MFS, Padua TA, Henriques MD, Morrot A, Savino W, Caruso-Neves C and Pinheiro AAS (2013), "Angiotensin II Is a New Component Involved in Splenic T Lymphocyte Responses during Plasmodium berghei ANKA Infection", Plos One., April, 2013. Vol. 8(4), pp. e62999. Public Library Science. [DOI] |
| Abstract: The contribution of T cells in severe malaria pathogenesis has been described. Here, we provide evidence for the potential role of angiotensin II (Ang II) in modulating splenic T cell responses in a rodent model of cerebral malaria. T cell activation induced by infection, determined by 3 to 4-fold enhancement in CD69 expression, was reduced to control levels when mice were treated with 20 mg/kg losartan (IC50 = 0.966 mg/kg/d), an AT(1) receptor antagonist, or captopril (IC50 = 1.940 mg/kg/d), an inhibitor of angiotensin-converting enzyme (ACE). Moreover, the production of interferon-gamma and interleukin-17 by CD4(+) T cells diminished 67% and 70%, respectively, by both treatments. Losartan reduced perforin expression in CD8(+) T cells by 33% while captopril completely blocked it. The upregulation in chemokine receptor expression (CCR2 and CCR5) observed during infection was abolished and CD11a expression was partially reduced when mice were treated with drugs. T cells activated by Plasmodium berghei ANKA antigens showed 6-fold enhance in AT(1) levels in comparison with naive cells. The upregulation of AT(1) expression was reduced by losartan (80%) but not by captopril. Our results suggest that the AT(1)/Ang II axis has a role in the establishment of an efficient T cell response in the spleen and therefore could participate in a misbalanced parasite-induced T cell immune response during P. berghei ANKA infection. |
BibTeX: @article{Silva2013, author = {Silva, J. L. and Souza, M. C. and Ferreira-DaSilva, C. T. and Silva, L. S. and Costa, M. F. S. and Padua, T. A. and Henriques, M. D. and Morrot, A. and Savino, W. and Caruso-Neves, C. and Pinheiro, A. A. S.}, title = {Angiotensin II Is a New Component Involved in Splenic T Lymphocyte Responses during Plasmodium berghei ANKA Infection}, journal = {Plos One}, publisher = {Public Library Science}, year = {2013}, volume = {8}, number = {4}, pages = {e62999}, doi = {10.1371/journal.pone.0062999} } |
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