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Borderline leprosy: in situ and cytokine profile in supernatant of mononuclear of cell culture

Venturini, J.
Fonte: Universidade Estadual Paulista (UNESP), Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP) Publicador: Universidade Estadual Paulista (UNESP), Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP)
Tipo: Artigo de Revista Científica Formato: 366-366
Português
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In order to contribute to a better understanding of cytokine participation in borderline leprosy, in the present study we determined - by in vitro and in situ examinations - the production of these cytokine mediation in non-treated borderline tuberculoid (BT) patients and borderline lepromatous (BL) patients. Seven non-treated BT patients, 12 non-treated BL patients, besides 19 healthy individuals (control group), were evaluated. Peripheral blood mononuclear cells (PBMC) were stimulated or not with specific-M. leprae stimulus (whole and sonicated M. leprae antigens) and a non-specific stimulus. After 48 hours, supernatant was collected for TNF-alpha, IFN-gamma, IL-10 and TGF-beta1 cytokine determination by ELISA. Biopsies from cutaneous lesions were submitted to histological analysis and hematoxylin-eosin and Fite-Faraco stainings; the sections then underwent iNOS, IL-10 and TGF-beta1 in situ detection by immunohistochemistry. Cytokine quantification in PBMC supernatants from patients showed that BT patients produced higher levels of IFN-gamma. Compared to healthy individuals, both borderline patient groups produced lower levels of TGF-beta1 while BL patients generated lower IL-10 levels. The in situ iNOS expression was higher in BT patients compared to BL individuals. on the order hand...

Evaluation of the Effects of Endodontic Materials on Fibroblast Viability and Cytokine Production

Gomes-Filho, Joao Eduardo; Watanabe, Simone; Gomes, Alessandra Cristina; Faria, Max Douglas; Lodi, Carolina Simonetti; Penha Oliveira, Sandra Helena
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 1577-1579
Português
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Introduction: Recently, a new sealer composed of Portland cement named Endo-CPM-Sealer was developed. The aim of this study was to investigate the effects of Endo-CPM-Sealer (EGEO SRL, Buenos Aires, Argentina), Sealapex (Sybron Endo, Glendora, CA), and Angelus MTA (Angelus, Londrina, Brazil) on cell viability and cytokine (interleukin [IL]-1 beta and IL-6) production by mouse fibroblasts. Methods: Millipore culture plate inserts with polyethylene tubes filled with materials were placed into 24-well cell culture plates with mouse fibroblasts. Cells cultured with only empty polyethylene tubes were used as the control. After 24 hours, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to evaluate the cell viability. For cytokine assay, mouse fibroblasts were incubated in 24-well flat-bottom plates with set material disks at the bottom. Cells cultured without the material disks served as the negative control. After 24 hours of incubation, culture media were collected for cytokine evaluation by using an enzyme-linked immunosorbent assay. The data were statistically analyzed by analysis of variance and Bonferroni correction. Results: Endo-CPM-Sealer, Sealapex, and Angelus MTA did not inhibit the cell viability. All materials induced IL-6 releasing...

Plasma cytokine response, lipid peroxidation and NF-κB activation in skeletal muscle following maximum progressive swimming

Oleto,A.F.; Sousa,L.P.; Barreto,T.O.; Cruz,J.S.; Penaforte,C.L.; Magalhães,J.C.; Sousa-Franco,J.; Pinto,K.M.C.; Campi-Azevedo,A.C.; Rocha-Vieira,E.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2011 Português
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Our objective was to determine lipid peroxidation and nuclear factor-κB (NF-κB) activation in skeletal muscle and the plasma cytokine profile following maximum progressive swimming. Adult male Swiss mice (N = 15) adapted to the aquatic environment were randomly divided into three groups: immediately after exercise (EX1), 3 h after exercise (EX2) and control. Animals from the exercising groups swam until exhaustion, with an initial workload of 2% of body mass attached to the tail. Control mice did not perform any exercise but were kept immersed in water for 20 min. Maximum swimming led to reactive oxygen species (ROS) generation in skeletal muscle, as indicated by increased thiobarbituric acid reactive species (TBARS) levels (4062.67 ±1487.10 vs 19,072.48 ± 8738.16 nmol malondialdehyde (MDA)/mg protein, control vs EX1). Exercise also promoted NF-κB activation in soleus muscle. Cytokine secretion following exercise was marked by increased plasma interleukin-6 (IL-6) levels 3 h post-exercise (P < 0.05). Interleukin-10 (IL-10) levels were reduced following exercise and remained reduced 3 h post-exercise (P < 0.05). Plasma levels of other cytokines investigated, monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α)...

Correlation of IL-6 and IL-10 production following bone marrow transplantation with donor cytokine gene polymorphisms

Visentainer,Jeane E. L.; Lieber,Sofia R.; Persoli,Ligia B. L.; Marques,Silvia B. D.; Vigorito,Afonso C.; Aranha,Francisco J. P.; Eid,Katia A. B.; Oliveira,Gislaine B.; Miranda,Eliana C. M.; Souza,Cármino A. de
Fonte: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular Publicador: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2008 Português
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Several candidate gene studies have demonstrated that genetic polymorphisms in cytokine genes contribute to variations in the levels of cytokines produced and this variation may influence the occurrence and severity of complications after stem cell transplantation (HSCT). In this work we compared the serum concentrations of TNF-α, IFN-γ, IL-6, IL-10, and TGF-β1 in 13 recipients following HSCT with the TNF-308, IFNG+874, IL6-174, IL10-1082,-819,-592, and TGFB1+869,+915 polymorphisms. Serum cytokine levels were assessed using commercial ELISA kits for TNF-α, IFN-γ, IL-6, IL-10, and TGF-β1 (BioSource®, Nivelles, Belgium, Europe). Donor/recipient genotypes for these cytokine polymorphisms were analyzed by polymerase chain reaction-sequence-specific primer (PCR-SSP) with the Cytokine Genotyping Primers Kit (One Lambda , Canoga Park, CA, USA). We found correlation between the levels of IL-6 and IL-10 concentrations following HSCT and the IL6-174 and IL10-1082,-819,-592 polymorphisms, but not for other cytokines investigated in this study. Those with genotypes associated with low production of IL-6 and IL-10 produced lower levels of these cytokines than those with genotypes associated with high or intermediate production of these cytokines (P < 0.05).

Kinetics of CD4 T Cell Cytokine Production, Chemokine Production and Activation after Influenza Vaccination

Li, Xi ; Mosmann, Tim R.
Fonte: Universidade de Rochester Publicador: Universidade de Rochester
Tipo: Tese de Doutorado
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Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Microbiology and Immunology, 2012.; The amount and timing of effector molecule secretion are tightly regulated in CD4 T cells during the immune response. T cell cytokine profiles have been studied extensively, but how chemokines are expressed during activation is less clear. This study showed that human CD4 T cells, activated with either influenza antigen or polyclonal stimulation, produce chemokines and cytokines with different kinetics. IL-2, IFNγ and TNFα were quickly induced, while chemokines CCL1, CCL3 and CCL4 were secreted later. Further analysis of sorted early cytokine positive cells showed that even though the IFNγ and IL-2 secreting cells have a preference to subsequently produce chemokines, the majority of chemokine producing cells did not secrete cytokines at early times. In addition to analyzing expression kinetics in individual cells, the kinetics of expansion of cytokine/chemokine-secreting cells during the human immune response to influenza vaccination were measured. The numbers of influenza-responsive CD4 T cells able to secrete chemokines increased transiently, 7 days after influenza vaccination, while the cytokine response did not change significantly. The response was then tracked more precisely by daily sampling...

Seminal plasma differentially regulates inflammatory cytokine gene expression in human cervical and vaginal epithelial cells

Sharkey, D.; Macpherson, A.; Tremellen, K.; Robertson, S.
Fonte: Oxford Univ Press Publicador: Oxford Univ Press
Tipo: Artigo de Revista Científica
Publicado em //2007 Português
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Exposure to semen elicits an inflammatory response in the female reproductive tract of rodents and other animals. The nature and regulation of any similar response in humans is poorly understood. This study investigated seminal plasma induction of inflammatory cytokine and chemokine gene regulation in human cervical and vaginal epithelial cells in vitro. Affymetrix microarray gene profiling revealed that inflammatory cytokine genes were prevalent among 317 known genes differentially expressed in immortalized ectocervical epithelial (Ect1) cells after incubation with pooled human seminal plasma. A dose- and time-dependent induction by seminal plasma of IL8, IL6, CSF2 and CCL2 mRNA expression in Ect1 cells was verified by quantitative RT–PCR. This was accompanied by increases in Ect1 secretion of immunoactive gene products IL-8, IL-6, GM-CSF and MCP-1. Similar cytokine responses were elicited in primary ectocervical epithelial cells. Endocervical epithelial (End1) and vaginal epithelial (Vk2) cells were less responsive to seminal fluid, with induction of IL-8 and MCP-1, but not GM-CSF or IL-6. In a panel of 10 seminal plasma samples, considerable variation in inflammatory cytokine-inducing activity was evident. These experiments show that seminal plasma can elicit expression of a range of inflammatory cytokines and chemokines in reproductive tract epithelia...

Cytokine receptor activation at the cell surface

Broughton, S.; Hercus, T.; Lopez, A.; Parker, M.
Fonte: Current Biology Ltd Publicador: Current Biology Ltd
Tipo: Artigo de Revista Científica
Publicado em //2012 Português
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Cytokines are well recognized for the pleiotropic nature of their signaling and biological activities on many cell types and their role in health and disease. Recent years have seen a steady stream of new cytokine receptor crystal structures including those that are activated by GM-CSF, type I interferon, and a variety of interleukins. Highlights include the observation of a dodecameric signaling complex for the GM-CSF receptor, electron microscopy imaging of an intact gp130/IL-6/IL-6Rα ternary receptor complex bound to its signal transducing Janus kinase and visualization of novel cytokine recognition mechanisms in the interleukin-17 and type I interferon families. This increasing knowledge in cytokine structural biology is driving new opportunities for developing novel therapies to modulate cytokine function in a diverse range of diseases including malignancies and chronic inflammation.; Sophie E Broughton, Timothy R Hercus, Angel F Lopez and Michael W Parker

Azithromycin suppresses P. gingivalis LPS induced pro-inflammatory cytokine and chemokine production (IL-6, IL-8, MCP-1 & GRO) by human gingival fibroblasts in vitro.

Doyle, Catherine Jane
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2014 Português
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Azithromycin is a macrolide antibiotic that is well known for its antibacterial properties, as well as possessing potential anti-inflammatory and immune modulating effects. This antibiotic has therefore been widely used in medicine for treating conditions ranging from inflammatory pulmonary diseases to dermatologic skin conditions. It has also been shown to be an effective antibiotic against most common periodontal pathogens and is used as an adjunct to treat periodontitis, a condition with bacterial aetiology and an inflammatory pathogenesis. Furthermore, periodontal case studies report regeneration of alveolar bone accompanied by significant reductions in inflammation have been achieved with azithromycin. The mechanisms however, by which these are achieved in the periodontium are largely unknown. This study aimed to determine the potential anti-inflammatory effect of azithromycin on cytokine and chemokine production by healthy human gingival fibroblasts (HGFs) that were stimulated by Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS). HGFs were isolated from healthy gingiva collected from three donors. The effects of azithromycin at concentrations ranging from 0.1 to 10 μg/mL were tested. Cytokine and chemokine protein levels were assessed using the Luminex® multiplex immunoassay. P. gingivalis LPS induced cytokine/chemokine (IL-6...

Untersuchungen zum Zusammenhang von Zytokinspiegeln im Serum und der T-Zell-Regeneration nach allogener Stammzelltransplantation; Investigations on the relationship of serum cytokine levels and T-cell regeneration after allogeneic stem cell transplantation

Guviraa, Chimgee
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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Die Zytokinspiegel von IL2, IL4, IL 6, IL10, TNF-a und IFN-g wurden im Serum von Patienten nach allogener Stammzelltransplantation mit CD34+ angereicherten Stammzellen von verwandten, HLA-nicht-identischen Familienspendern und HLA-identischen Fremdspendern im zeitlichen Verlauf untersucht. Es wurde überprüft, ob Zytokinmuster erkennbar sind, die mit einem günstigen klinischen Verlauf, schneller Regeneration von T-Zellen, dem Auftreten einer GvH oder einem Non-engraftment oder einer Abstoßung korreliert werden können. Ferner wurden die beiden Patientengruppen miteinander verglichen. Sämtliche Zytokine konnten bei der überwiegenden Zahl von Patienten nachgewiesen werden. Somit kann auch durch die alleinige Gabe von hochreinen Stammzellen ein Zytokinmilieu etabliert werden. Weitere hämatopoetische Zelltypen des Spenders, wie sie bei der konventionellen Knochenmarktransplantation in großer Menge verabreicht werden, scheinen hierfür nicht notwendig zu sein. Die Werte von Interleukin 2 lagen dabei in der Gruppe der Patienten mit haploidentischen Spendern mit schneller T-Zellerholung deutlich höher als bei Patienten mit schlechter T-Zellerholung. Darüber hinaus korrelierte der Wert signifikant mit der Anzahl an CD56+ NK-Zellen. Für Interleukin 4 konnte kein Zusammenhang mit einem der untersuchten Parameter gefunden werden. Interleukin 10 wurde in erhöhter Konzentration bei Patienten mit Non-engraftment und Abstoßung gefunden. In allen Fällen ging es dabei mit erhöhter Körpertemperatur einher...

Pronounced regulatory T cell activity in human schistosomiasis:differences in T cell proliferation and cytokine responses before and after treatment with Praziquantel; Vermehrte regulatorische T-Zell-Aktivität in menschlicher Bilharziose: Unterschiede in T-Zell-Proliferation und Zytokin-Antworten vor und nach der Behandlung mit Praziquantel

Schmiedel, Yvonne
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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Schistosomiasis is a parasitic disease, which occurs predominantly in Sub - Saharan Africa. While annually an estimated 230 Million individuals become affected, mainly children are at risk of contracting this disease. S. haematobium, one of the 5 main types of Schistosomiasis, is the only one affecting the urinary tract system. With its hot and humid climate as well as often poor water sanitation facilities Gabon is widely affected by S. haematobium. Currently the disease is still effectively treated with the anti-helminth medication Praziquantel, though rapid re-infection compromises long-term effectiveness of this therapy. Hence, life-long immunity via an effective vaccine would be desirable. A number of studies involving various infectious diseases showed a strong correlation between T-reg cells and prolonged disease. This led to the assumption that T-reg cells could play a key role in the immune process once the host becomes infected with the parasite. This study was dedicated to investigate the role of T-reg cells in children infected with S. haematobium in a high prevalence area. Measuring and comparing cell proliferative- and cytokine responses prior and after depletion of T-reg cells allowed to evaluate the cells’ effects. Measurements were carried out before and 6 weeks after treatment allowing to establish any treatment effect on T-reg cells. After identifying T-reg cells as CD4+ CD25high Foxp3+ cells...

Molecular basis of cytokine receptor activation

Lopez, A.; Hercus, T.; Ekert, P.; Littler, D.; Guthridge, M.; Thomas, D.; Ramshaw, H.; Stomski, F.; Perugini, M.; D'Andrea, R.; Grimbaldeston, M.; Parker, M.
Fonte: Taylor & Francis Inc Publicador: Taylor & Francis Inc
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
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Cytokines are secreted soluble peptides that precisely regulate multiple cellular functions. Amongst these the GM-CSF/IL-3/IL-5 family of cytokines controls whether hematopoietic cells will survive or apoptose, proliferate, differentiate, migrate, or perform effector functions such as phagocytosis or reactive oxygen species release. Their potent and pleiotropic activities are mediated through binding to high affinity membrane receptors at surprisingly low numbers per cell. Receptor binding triggers a cascade of intracellular signaling events, including reversible phosphorylation of receptor subunits and associated signaling molecules, leading to multiple biological responses, with the prevention of apoptosis or "cell survival" being a key cellular function that underpins all others. Many chronic inflammatory diseases and a number of haematological malignancies are driven by deregulated GM-CSF, IL-3, or IL-5 cytokine receptor signaling, highlighting their importance in disease. A major step in understanding how these cytokine receptors function is to elucidate their three dimensional structure and to relate this to the many signaling pathways emanating from their receptors. We have recently solved the structure of the human GM-CSF receptor complexed to GM-CSF which revealed distinct forms of receptor assembly: a hexamer that comprises two molecules each of GM-CSF...

THE IMPACT OF VIRUS INFECTION IN DEREGULATION OF CYTOKINE PRODUCTION UPON SECONDARY BACTERIAL INFECTION

Mehta, DIVYA
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado
Português
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Dendritic cells (DCs) secrete cytokines such as interleukin-23 (IL-23) when stimulated with certain Toll-like receptor (TLR) agonists and infected with pathogens such as P. aeruginosa. IL- 23 is a proinflammatory cytokine that plays a critical role in the proliferation and differentiation of the IL-17 producing Th17- CD4 T helper cells. The lack of efficient cytokine production from antigen-presenting cells, such as DCs, can impact CD4 differentiation and thus impair the immune responses against pathogens. Clearance of some bacterial infections, such as Klebsiella pneumonia and Listeria monocytogenes has been shown to be dependent on the induction of IL-23 and therefore, deregulation of these cytokines as a direct result of virus infection may impede immune responses to secondary infections. Here, an inhibition of TLR ligand or P. aeruginosa-induced IL- 23 expression in Lymphocytic Choriomeningitis Virus (LCMV)-infected bone marrow-derived dendritic cells (BMDCs) has been demonstrated, indicating that an important function of these cells is disrupted during virus/bacterial coinfection. While production of TNF-α was unaffected in LPS stimulated cells, TNF-α was significantly inhibited in bacterium infected cells by LCMV. Type I IFN in LPS or LCMV infected cell was not detected and therefore...

Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status

ARAUJO-PIRES,Ana Claudia; FRANCISCONI,Carolina Favaro; BIGUETTI,Claudia Cristina; CAVALLA,Franco; ARANHA,Andreza Maria Fabio; LETRA,Ariadne; TROMBONE,Ana Paula Favaro; FAVERI,Marcelo; SILVA,Renato Menezes; GARLET,Gustavo Pompermaier
Fonte: Faculdade De Odontologia De Bauru - USP Publicador: Faculdade De Odontologia De Bauru - USP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/2014 Português
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Previous studies demonstrate that the balance between pro- and anti-inflammatory mediators determines the stable or progressive nature of periapical granulomas by modulating the balance of the osteoclastogenic factor RANKL and its antagonist OPG. However, the cytokine networks operating in the development of periapical lesions are quite more complex than what the simple pro- versus anti-inflammatory mediators' paradigm suggests. Here we simultaneously investigated the patterns of Th1, Th2, Th9, Th17, Th22, Thf, Tr1 and Tregs cytokines/markers expression in human periapical granulomas. Methods: The expression of TNF-α, IFN-γ, IL-17A, IL23, IL21, IL-33, IL-10, IL-4, IL-9, IL-22, FOXp3 markers (via RealTimePCR array) was accessed in active/progressive (N=40) versus inactive/stable (N=70) periapical granulomas (as determined by RANKL/OPG expression ratio), and also to compare these samples with a panel of control specimens (N=26). A cluster analysis of 13 cytokine levels was performed to examine possible clustering between the cytokines in a total of 110 granulomas. Results: The expression of all target cytokines was higher in the granulomas than in control samples. TNF-α, IFN-γ, IL-17A and IL-21 mRNA levels were significantly higher in active granulomas...

T helper 1/T helper 2 cytokine imbalance in respiratory syncytial virus infection is associated with increased endogenous plasma cortisol

Gaggero, Aldo; Arredondo, Sonia M.; Díaz, Patricia V.; Bono Merino, María Rosa; Pinto, Ricardo A.
Fonte: AMER ACAD PEDIATRICS Publicador: AMER ACAD PEDIATRICS
Tipo: Artículo de revista
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OBJECTIVE. Cellular immunity has classically been described as the defense mechanism for viral infections. The development of cellular or humoral immune responses will depend on a repertoire of cytokines produced by numerous cells, including CD4(+) and CD8(+) T cells. These lymphocytes can be subdivided into 2 subsets, T helper 1 ( Th1) and Th2, on the basis of the cytokine profiles they synthesize. Type 1 T cells produce interferon gamma( IFN-gamma), an essential cytokine in the viral cell-mediated immune response. Th2 cells selectively produce interleukin 4 ( IL-4) and IL-5 that participate in the development of humoral immunity and have a prominent role in immediate-type hypersensitivity. An imbalance in the Th1/Th2 cytokine immune response has been related to pathogenesis of the respiratory syncytial virus ( RSV) bronchiolitis and to the severity of the infection. Glucocorticosteroids have a role in inhibiting the IFN-gamma response, acting directly on T cells or indirectly through IL-12. In this way, an increase in plasma cortisol would induce a decrease in the Th1 products with the imbalance between Th1/Th2 cytokines and a shift to Th2 response. We hypothesized that there is a relationship among endogenous cortisol response in acute RSV infection...

Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo

Field, Sarah L.; Dasgupta, Tathagata; Cummings, Michele; Savage, Richard S.; Adebayo, Julius; McSara, Hema; Gunawardena, Jeremy; Orsi, Nicolas M.
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
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Background: Cytokine-hormone network deregulations underpin pathologies ranging from autoimmune disorders to cancer, but our understanding of these networks in physiological/pathophysiological states remains patchy. We employed Bayesian networks to analyze cytokine-hormone interactions in vivo using murine lactation as a dynamic, physiological model system. Results: Circulatory levels of estrogen, progesterone, prolactin and twenty-three cytokines were profiled in post partum mice with/without pups. The resultant networks were very robust and assembled about structural hubs, with evidence that interleukin (IL)-12 (p40), IL-13 and monocyte chemoattractant protein (MCP)-1 were the primary drivers of network behavior. Network structural conservation across physiological scenarios coupled with the successful empirical validation of our approach suggested that in silico network perturbations can predict in vivo qualitative responses. In silico perturbation of network components also captured biological features of cytokine interactions (antagonism, synergy, redundancy). Conclusion: These findings highlight the potential of network-based approaches in identifying novel cytokine pharmacological targets and in predicting the effects of their exogenous manipulation in inflammatory/immune disorders. Electronic supplementary material The online version of this article (doi:10.1186/s12918-015-0226-3) contains supplementary material...

Dissociation of T helper type 2 cytokine-dependent airway lesions from signal transducer and activator of transcription 6 signalling in experimental chronic asthma

Foster, Paul S; Webb, Dianne; Yang, Ming; Herbert, John; Kumar, Rakesh K
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
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Background: Type 2 T helper lymphocytes (Th2 cells) and their cytokine products are important in the pathogenesis of asthma. Objective: To examine the contribution of the signal transducer and activator of transcription (STAT) 6 pathway, involved in Th2 cytokine signalling, to the development of lesions of chronic asthma. Methods: BALB/c mice sensitized to ovalbumin were chronically challenged by inhalational of low mass concentrations of antigen for 6 weeks. Airway lesions in wild-type mice were compared with those in STAT6-deficient mice and in IL-4/13 double-deficient mice by histomorphometry and immunohistochemistry. Airway responses to methacholine were evaluated by whole-body plethysmography. Cytokine production by peribronchial lymph node cells was quantified by enzyme immunoassay. Results: STAT6-/- mice developed a variety of airway lesions that were at least equivalent to those in wild-type mice, including accumulation of intraepithelial eosinophils and of chronic inflammatory cells in the lamina propria, subepithelial fibrosis and epithelial thickening. In addition, STAT6-/- mice exhibited exaggerated airway hyper-reactivity (AHR) compared to wild-type animals. This was despite a shift from a Th2 to a Th1 pattern of immunoglobulin production by plasma cells in the inflammatory infiltrate and diminished mucous cell hyperplasia/metaplasia...

Polarized type 1 cytokine response and cell-mediated immunity determine genetic resistance to mousepox

Chaudhri, Geeta; Panchanathan, Vijay; Buller, R Mark; van den Eertwegh, Alfons; Claassen, E; Zhou, Jiansheng; De Chazal, Rosalind; Laman, J; Karupiah, Gunasegaran
Fonte: National Academy of Sciences (USA) Publicador: National Academy of Sciences (USA)
Tipo: Artigo de Revista Científica
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Ectromelia virus (ECTV), a natural mouse pathogen and an orthopoxvirus, has been used to investigate the correlation between polarized type 1 or type 2 immune responses and resistance to disease in poxvirus infections by using well defined resistant and susceptible mouse strains. Our data show that distinct differences exist in the cytokine profiles expressed in resistant and susceptible mice infected with ECTV. Resistant C57BL/6 mice generate a type 1 cytokine response [IFN-γ, IL-2, and tumor necrosis factor (TNF)], within the first few days of infection, which is associated with strong cytotoxic T lymphocyte response (CTL) and recovery from ECTV infection. Susceptible strains of mice (BALB/c and A/J) on the other hand generate a type 2 cytokine response (IL-4 but little or no IFN-γ and IL-2), which is associated with a weak or an absent CTL response, resulting in uncontrolled virus replication and death. Although deletion of IL-4 function alone did not change the outcome of infection in susceptible mice, the loss of IFN-γ function in resistant mice abrogated natural killer (NK) cell and CTL effector functions resulting in fulminant disease and 100% mortality. Therefore, a clear link exists between the early production of specific type 1 cytokines...

Replication restricted vaccinia as a cytokine gene therapy vector in cancer: persistent transgene expression despite antibody generation

Mukherjee, Sutapa; Haenel, Thomas; Himbeck, Robyn; Scott, Bernadette; Ramshaw, Ian; Lake, Richard A; Harnett, J; Phillips, Peter; Morey, Sue; Smith, David; Davidson, J Andrew; Musk, Arthur W; Robinson, Bruce
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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Background: As antitumoral immunity requires the generation of local immunity directed against tissue proteins, we attempted to recreate within tumors the same environment found within tissues affected by autoimmune diseases (i.e., prolonged cytokine expression). Vaccinia virus (VV) has not been widely used as a cytokine gene therapy vector because of presumed high immunogenicity that would likely make repeated injections impossible; therefore, we modified it by inserting the cytokine gene into the thymidine kinase region, rendering it replication-restricted. The cytokine chosen was human interleukin-2 (IL-2), a molecule with powerful antitumoral effects. Methods: Six patients with the treatment-resistant tumor malignant mesothelioma received intratumoral (i.t.) VV-IL-2 therapy for 12 weeks by injection of 107 plaque-forming units of W-IL-2 per dose. Serial tumor biopsies, sputum, urine, and blood samples were tested for VV-IL-2 mRNA expression; VV culture and T-cell infiltrates were evaluated by immunohistochemistry. Patients and of patients were monitored for changes in VV immunoglobulin G (IgG) levels and clinical evidence of VV infection. Results: VV-IL-2 was not excreted and was only cultured in one patient from tumor biopsies. A T-cell infiltrate was detected in 50% of tumor biopsies. VV-IL-2 mRNA expression was highest on days 1-3 postinjection and was detected for up to 3 weeks after each injection even though VV IgG levels rose in all patients. No significant toxicities...

The role of architectural transcription factors in cytokine gene transcription

Shannon, M Frances; Coles, Leeanne; Attema, Joanne; Diamond, Peter
Fonte: Federation of American Societies for Experimental Biology Publicador: Federation of American Societies for Experimental Biology
Tipo: Artigo de Revista Científica
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The strict control of cytokine gene transcription is required for the correct regulation of an immune response. Cytokine gene transcription is generally inducible and can also be cell-type specific. Promoter and enhancer regions that control the expression of these genes assemble complex arrays of transcription factors known as enhanceosomes. One important aspect of the organization of these multi-protein complexes is the presence of proteins known as architectural transcription factors. Architectural proteins influence structural aspects of enhanceosomes through protein:DNA as well as protein:protein interactions. The high mobility group I(Y) and the cold shock domain families of architectural proteins have been shown to play roles in cytokine gene transcription and will be discussed here. These families of proteins interact with specific structural features of DNA, modulate transcription factor binding to DNA, and interact directly with other transcription factors. The mechanisms by which they affect inducible cytokine gene transcription will be discussed.

Cytokine-Related Genes Identified From the RIKEN Full-Length Mouse cDNA Data Set

Brusic, Vladimir; Pillai, Rekha; Silva, Diego; Petrovsky, Nikolai; Schonbach, Christian
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
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To identify novel cytokine-related genes, we searched the set of 60,770 annotated RIKEN mouse cDNA clones (FANTOM2 clones), using keywords such as cytokine itself or cytokine names (such as interferon, interleukin, epidermal growth factor, fibroblast growth factor, and transforming growth factor). This search produced 108 known cytokines and cytokine-related products such as cytokine receptors, cytokine-associated genes, or their products (enhancers, accessory proteins, cytokine-induced genes). We found 15 clusters of FANTOM2 clones that are candidates for novel cytokine-related genes. These encoded products with strong sequence similarity to guanylate-binding protein (GBP-5), interleukin-1 receptor-associated kinase 2 (IRAK-2), interleukin 20 receptor α. isoform 3, a member of the interferon-inducible proteins of the Ifi 200 cluster, four members of the membrane-associated family 1-8 of interferon-inducible proteins, one p27-like protein, and a hypothetical protein containing a Toll/Interleukin receptor domain. All four clones representing novel candidates of gene products from the family contain a novel highly conserved cross-species domain. Clones similar to growth factor-related products included transforming growth factor β-inducible early growth response protein 2 (TIEG-2)...