Página 1 dos resultados de 8694 itens digitais encontrados em 0.029 segundos

Protein-Energy Malnutrition Modifies the Production of Interleukin-10 in Response to Lipopolysaccharide (LPS) in a Murine Model

FOCK, Ricardo Ambrosio; VINOLO, Marco Aurelio Ramirez; CRISMA, Amanda Rabello; NAKAJIMA, Karina; ROGERO, Marcelo Macedo; BORELLI, Primavera
Fonte: CENTER ACADEMIC PUBL JAPAN Publicador: CENTER ACADEMIC PUBL JAPAN
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
55.96%
Malnutrition modifies resistance to infection by impairing a number of physiological processes including hematopoesis and the immune response. In this study, we examined the production of Interleukin-4 (IL-4) and IL-10 in response to lipopolysaccharide (LPS) and also evaluated the cellularity of the blood, bone marrow, and spleen in a mouse model of protein-energy malnutrition. Two-month-old male Swiss mice were subjected to protein-energy malnutrition (PEM) with a low-protein diet (4%) as compared to the control diet (20%). When the experimental group lost approximately 20% of their original body weight, the animals from both groups received 1.25 mu g of LPS intravenously. The Cells ill the blood, bone marrow, and spleen were counted, and circulating levels of IL-4 and IL-10 were evaluated in animals stimulated with LPS. Cells from the spleen, bone marrow, and peritoneal cavity of non-inoculated animals were collected for Culture to evaluate the production of IL-4 and IL-10 after stimulating these cells with 1.25 mu g of LPS in vitro. Malnourished animals presented leucopenia and a severe reduction in bone marrow, spleen, and peritoneal cavity cellularity before and after Stimulus with LPS. The circulating levels of IL-10 were increased in malnourished animals inoculated with LPS when compared to control animals...

Interferon-gamma, interleukin-10, intercellular adhesion molecule-1, and chemokine receptor 5, but not interleukin-4, attenuate the development of periapical lesions

ROSSI, Andiara De; ROCHA, Lenaldo B.; ROSSI, Marcos A.
Fonte: ELSEVIER SCIENCE INC Publicador: ELSEVIER SCIENCE INC
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
55.91%
This study examines the role of Th1 (interferon-gamma [IFN-gamma]) and Th2 (interleukin-4 [IL-4] and IL-10) cytokines, an intercellular adhesion molecule (ICAM-1), and a chemokine receptor (CCR5) in the pathogenesis of periapical lesions at different stages of development in knockout mice. For lesion induction, the first molar was opened and inoculated with 4 bacterial strains and left open to the oral environment. After 21 and 42 days, the IFN-gamma, IL-10, ICAM-1, and CCR5 knockout animals presented periapical lesions larger than those of wild-type animals. There was no statistically significant difference between periapical lesions induced in IL-4 knockout and wild-type animals during the periods evaluated. Our findings suggest an important role for IFN-gamma, IL-10, ICAM-1, and CCR5 in the pathogenesis of experimentally induced pulp infection and bone destruction as endogenous suppressor of periapical lesion development, whereas IL-4 appears to present a nonsignificant effect on periapical lesion modulation.

Interleukin-4 Modulates the Inflammatory Response in Ifosfamide-Induced Hemorrhagic Cystitis

Bulcao Macedo, Francisco Yuri; Cajaseiras Mourao, Livia Talita; Freitas, Helano Carioca; Lima-Junior, Roberto C. P.; Tenazoa Wong, Deysi Viviana; Oria, Reinaldo Barreto; Vale, Mariana L.; Casto Brito, Gerly Anne; Cunha, Fernando Q.; Ribeiro, Ronaldo A.
Fonte: SPRINGER/PLENUM PUBLISHERS; NEW YORK Publicador: SPRINGER/PLENUM PUBLISHERS; NEW YORK
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
55.94%
We investigated whether interleukin-4 (IL-4) is present and capable of reducing inflammatory changes seen in ifosfamide-induced hemorrhagic cystitis. Male Swiss mice were treated with saline or ifosfamide alone or ifosfamide with the classical protocol with mesna and analyzed by changes in bladder wet weight (BWW), macroscopic and microscopic parameters, exudate, and hemoglobin quantification. In other groups, IL-4 was administered intraperitoneally 1 h before ifosfamide. In other experimental groups, C57BL/6 WT (wild type) and C57BL/6 WT IL-4 (-/-) knockout animals were treated with ifosfamide and analyzed for changes in BWW. Quantification of bladder IL-4 protein by ELISA in control, ifosfamide-, and mesna-treated groups was performed. Immunohistochemistry to tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) as well as protein identification by Western blot assay for inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was carried out on ifosfamide- and IL-4-treated animals. In other experimental groups, antiserum against IL-4 was given 30 min before ifosfamide. In IL-4-treated animals, the severity of hemorrhagic cystitis was significantly milder than in animals treated with ifosfamide only...

Interleukin-4 and interleukin-13 inhibit the expression of leukemia inhibitory factor and interleukin-11 in fibroblasts

Souza, Pedro P. C.; Palmqvist, Py; Lundberg, Pernilla; Lundgren, Inger; Hanstrom, Lennart; Souza, Joao A. C.; Conaway, H. Herschel; Lerner, Ulf H.
Fonte: Pergamon-Elsevier B.V. Ltd Publicador: Pergamon-Elsevier B.V. Ltd
Tipo: Artigo de Revista Científica Formato: 601-610
Português
Relevância na Pesquisa
56%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Cytokines produced by inflammatory or resident mesenchymal cells play important modulatory roles in the pathogenesis of inflammation induced bone loss. In the present study, the effects of IL-4 and IL-13 on the expression of three osteotropic cytokines in the IL-6 family expressed in human gingival fibroblasts were studied. IL-4R alpha and IL-13R alpha 1 mRNA were constitutively expressed in human gingival fibroblasts. The inflammatory cytokines IL-1 beta and TNF-alpha increased expression of IL-5, LIF, and IL-11 mRNA and protein in the gingival fibroblasts. Addition of IL-4 or IL-13 had no effect on IL-6 expression, but significantly inhibited LIF and IL-11 mRNA and protein stimulated by IL-1 beta and TNF-alpha. No involvement of NF-kappa B or STAT1 was observed in the inhibition. STAT6 was phosphorylated at Y641 by treatment with IL-4 and knockdown of STAT6 with siRNA decreased the inhibition of IL-11 and LIF expression by IL-4 in IL-1 beta and TNF-alpha stimulated cells. This study suggests that activation of STAT6 by IL-4 and IL-13, through type 2 IL-4 receptors, inhibits production of IL-11 and LIF stimulated by IL-1 beta and TNF-alpha in human gingival fibroblasts. A negative modulatory role of IL-4 and IL-13 in osteotropic cytokine production could be a mechanism playing an important inhibitory role in inflammation induced periodontitis. (C) 2011 Elsevier Ltd. All rights reserved.

Association of Interleukin 4 Gene Polymorphisms With Dental Implant Loss

Pigossi, Suzane C.; Alvim-Pereira, Fabiano; Alvim-Pereira, Claudia C. K.; Trevilatto, Paula C.; Scarel-Caminaga, Raquel M.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica Formato: 723-731
Português
Relevância na Pesquisa
65.88%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Processo FAPESP: 09/09932-8; Purpose: The purpose of this study was to investigate the association between interleukin 4 (IL4) polymorphisms/haplotypes and dental implant loss.Materials and Methods: Two hundred and seventy eight (n = 278) unrelated patients were divided into 2 groups: (1) control group (C) composed of 186 individuals presenting at least 1 osseointegrated implant and (2) study group (S) composed of 94 individuals presenting at least 1 implant loss. After DNA collection, IL4 polymorphisms were investigated by polymerase chain reaction (PCR)restriction fragment length polymorphism and for the variable number of tandem repeat (VNTR) only by PCR.Results: No association between alleles/genotypes of -590 (C/T) (P = 0.9704/P = 0.5992) and VNTR (P = 0.7155/P = 0.8789) polymorphisms and implant loss were found between the groups. Regarding +33 (C/T) polymorphism, no difference was found in genotype frequency (P = 0.1288), but the C allele was associated with implant loss (P = 0.0236, odds ratio = 1.61, 95% confidence interval = 1.1-2.4). Haplotype analysis showed no statistical differences between the groups.Conclusion: The C allele of the +33 (C/T) polymorphism in the IL4 gene was associated with susceptibility to dental implant loss in Brazilians in the studied population.

Study of polymorphisms in the interleukin-4 and IL-4 receptor genes in a population of Brazilian patients with multiple sclerosis

Quirico-Santos,Thereza; Suppiah,Vijayaprakash; Heggarty,Shirley; Caetano,Regina; Alves-Leon,Soniza; Vandenbroeck,Koen
Fonte: Academia Brasileira de Neurologia - ABNEURO Publicador: Academia Brasileira de Neurologia - ABNEURO
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2007 Português
Relevância na Pesquisa
55.82%
This study aimed to investigate in a population of Brazilian patients with multiple sclerosis (MS) single-nucleotide polymorphisms (SNP) in the promoter region of IL4 (*33C-T) and receptor IL4R (*Q551R A-G) genes proposed to interfere with disease progression. No significant differences were observed in either of the SNPs investigated between healthy controls (n=135) and MS patients (n=129). However, the IL4+33 TT genotype was significantly (p=0.039) higher in African descendants MS (AF-MS= 9.09%) than in Caucasian MS (CA-MS= 1.35%). It was also observed a significant (p=0.016) increase for the IL4R* Q551R CC genotype in AF-MS compared to those of Caucasian ethnicity (AF-MS= 21.62%; CA-MS= 4.35%). These results suggest that IL4+33 and IL4R*Q551 polymorphisms may have a disease-promoting role of TH2 mediators in African MS descendants. Additionally neither IL4 nor IL4R genes are susceptibility factors for Brazilian MS but may be able to modify ethnicity-dependent disease risk and penetrance of susceptibility factors.

Interleukin-4 and interleukin-5 as targets for the inhibition of eosinophilic inflammation and allergic airways hyperreactivity

Foster,Paul S; Hogan,Simon P; Matthaei,Klaus I; Young,Ian G
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/1997 Português
Relevância na Pesquisa
55.95%
Clinical and experimental investigations suggest that allergen-specific CD4+ T-cells, IgE and the cytokines IL-4 and IL-5 play central roles in initiating and sustaining an asthmatic response by regulating the recruitment and/or activation of airways mast cells and eosinophils. IL-5 plays a unique role in eosinophil development and activation and has been strongly implicated in the aetiology of asthma. The present paper summarizes our recent investigations on the role of these cytokines using cytokine knockout mice and a mouse aeroallergen model. Investigations in IL-5-/- mice indicate that this cytokine is critical for regulating aeroallergen-induced eosinophilia, the onset of lung damage and airways hyperreactivity during allergic airways inflammation. While IL-4 and allergen-specific IgE play important roles in the regulation of allergic disease, recent investigations in IL4-/- mice suggest that allergic airways inflammation can occur via pathways which operate independently of these molecules. Activation of these IL-4 independent pathways are also intimately associated with CD4+ T-cells, IL-5 signal transduction and eosinophilic inflammation. Such IL-5 regulated pathways may also play a substantive role in the aetiology of asthma. Thus...

Interleukin-4 production in BALB/c mice immunized with Anisakis simplex

Perteguer,María Jesús; Cuéllar,Carmen
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/10/2001 Português
Relevância na Pesquisa
55.9%
We investigated the interleukin (IL-4) levels in BALB/c mice immunized with Anisakis extract in single or multiple doses and in mice orally infected with a larva. From animals immunized maximum responses were obtained with the multiple doses with an only IL-4 peak. Conversely, in the mice inoculated with a larva per os, the IL-4 levels showed two peaks of different rates.

Induction of oral tolerance and the effect of interleukin-4 on murine skin allograft rejection

Dettino,A.L.A.; Duarte,A.J.S.; Sato,M.N.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2004 Português
Relevância na Pesquisa
65.9%
We studied the effect of oral and portal vein administration of alloantigens on mouse skin allograft survival. Graft receptor BALB/c mice received spleen cells (30, 90, 150 or 375 x 10(6)) from donor C57BL/6 mice intragastrically on three successive days, starting seven days before the skin graft. Allograft survival was significantly increased with the feeding of 150 x 10(6) allogeneic spleen cells by one gavage (median survival of 12 vs 14 days, P <= 0.005) or when 300 x 10(6) cells were given in six gavage (12 vs 14 days, P < 0.04). A similar effect was observed when 150 x 10(6) spleen cells were injected into the portal vein (12 vs 14 days, P <= 0.03). Furthermore, prolonged allograft survival was observed with subcutaneous (12 vs 16 days, P <= 0.002) or systemic (12 vs 15 days, P <= 0.016) application of murine interleukin-4 (IL-4), alone or in combination with spleen cell injection into the portal vein (12 vs 18 days, P <= 0.0018). Taken together, these results showed that tolerance induction with spleen cells expressing fully incompatible antigens by oral administration or intraportal injection partially down-modulates skin allograft rejection. Furthermore, these findings demonstrated for the first time the effect of subcutaneous or systemic IL-4 application on allograft skin survival suggesting its use as a beneficial support therapy in combination with a tolerance induction protocol.

Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist.

Vannier, E; Miller, L C; Dinarello, C A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/05/1992 Português
Relevância na Pesquisa
46.08%
Interleukin 1 receptor antagonist (IL-1ra), a naturally occurring polypeptide with amino acid sequence homology to interleukin 1 alpha (IL-1 alpha) and interleukin 1 beta (IL-1 beta), prevents Escherichia coli-induced shock and death. Both IL-1 and IL-1ra are produced by monocytes stimulated with lipopolysaccharide (LPS). Because interleukin 4 (IL-4) suppresses IL-1 production, we investigated whether IL-4 modulated IL-1ra synthesis in LPS-stimulated human peripheral blood mononuclear cells. IL-1 beta and IL-1ra were measured by specific RIAs. IL-4 alone (0.01-100 ng/ml) did not stimulate IL-1 beta synthesis but rather induced IL-1ra (4.82 +/- 0.94 ng/ml). LPS induced synthesis of both IL-1 beta (6.67 +/- 1.06 ng/ml) and IL-1ra (10.77 +/- 2.79 ng/ml). IL-4 suppressed LPS-induced IL-1 beta mRNA accumulation and synthesis. However, IL-4 acted synergistically with LPS in inducing IL-1ra. IL-4 enhanced LPS-induced IL-1ra mRNA accumulation 4-fold and IL-1ra protein synthesis nearly 2-fold. Moreover, IL-1ra mRNA levels were maximal after 6 hr of exposure to LPS but peaked within the first 3 hr in the presence of IL-4. IL-4 added as late as 12 hr after LPS stimulation still enhanced IL-1ra synthesis. In human peripheral blood mononuclear cells stimulated with IL-1 alpha...

Regulation of 15-lipoxygenase expression in lung epithelial cells by interleukin-4.

Brinckmann, R; Topp, M S; Zalán, I; Heydeck, D; Ludwig, P; Kühn, H; Berdel, W E; Habenicht, J R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/08/1996 Português
Relevância na Pesquisa
46.07%
We have studied the expression of the 15-lipoxygenase gene in various permanent mammalian cell lines in response to interleukins-4 and -13, and found that none of the cell lines tested expressed 5-, 12- or 15-lipoxygenase when cultured under standard conditions. However, when the lung carcinoma cell line A549 was maintained in the presence of either interleukin for 24 h or more, we observed a major induction of 15-lipoxygenase, as indicated by quantification of 15-lipoxygenase mRNA, by immunohistochemistry, by immunoblot analysis and by enzyme activity assays. This effect was 15-lipoxygenases-specific, since expression of 5- and 12-lipoxygenases remained undetectable. The time course of interleukin-4 treatment indicated maximal accumulation of both 15-lipoxygenase mRNA and functional protein after 48 h. Binding studies revealed that A549 cells express about 2100 high-affinity interleukin-4 binding sites per cell. The interleukin-4 mutant Y124D, which is capable of binding to the interleukin-4 receptor but is unable to trigger receptor activation, counteracted the effect of the wild-type cytokine. Other cell lines, including several epithelial cells and various monocytic cell lines expressing comparable numbers of interleukin-4 receptors...

Interleukin-4 induces foreign body giant cells from human monocytes/macrophages. Differential lymphokine regulation of macrophage fusion leads to morphological variants of multinucleated giant cells.

McNally, A. K.; Anderson, J. M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1995 Português
Relevância na Pesquisa
46.06%
Interleukin-4 induced the formation of foreign body-type giant multinucleated cells from human monocyte-derived macrophages, an effect that was optimized with either granulocyte-macrophage colony-stimulating factor or interleukin-3, dependent on the concentration of interleukin-4, and specifically prevented by anti-interleukin-4. Very large foreign body giant cells and, predominantly, giant cell syncytia with randomly arranged nuclei and extensive cytoplasmic spreading (285 +/- 121 nuclei and 1.151 +/- 0.303 mm2 per syncytium) were consistently obtained. Under otherwise identical culture conditions, relatively much smaller Langhans-type giant cells with circularly arranged nuclei were induced with a previously described combination of interferon-gamma plus granulocyte-macrophage colony-stimulating factor or interleukin-3 (16 +/- 6 nuclei and 0.033 +/- 0.013 mm2 per giant cell); their formation was prevented by anti-interferon-gamma but not by anti-interleukin-4. Similar rates of macrophage fusion were obtained in both culture systems (72 +/- 5% and 74 +/- 6%, respectively), but these two morphological variants did not occur simultaneously or form from one another within the 10-day culture period. These findings demonstrate that interleukin-4 is a potent human macrophage fusion factor and that differential regulation of macrophage fusion by interleukin-4 and interferon-gamma may lead to morphological variants of multinucleated giant cells.

The Influence of Interleukin-4 on Ligament Healing

Chamberlain, Connie S; Leiferman, Ellen M; Frisch, Kayt E; Wang, Sijian; Yang, Xipei; Brickson, Stacey L; Vanderby, Ray
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.06%
Despite a complex cascade of cellular events to reconstruct the damaged extracellular matrix, ligament healing results in a mechanically inferior scarred ligament. During normal healing, granulation tissue expands into any residual normal ligamentous tissue (creeping substitution), resulting in a larger region of healing, greater mechanical compromise, and an inefficient repair process. To control creeping substitution and possibly enhance the repair process, the anti-inflammatory cytokine, interleukin-4 (IL-4) was administered to rats prior to and after rupture of their medial collateral ligaments. In vitro experiments demonstrated a time-dependent effect on fibroblast proliferation after interleukin-4 treatment. In vivo treatments with interleukin-4 (100 ng/ml i.v.) for 5 days resulted in decreased wound size and type III collagen and increased type I procollagen, indicating a more regenerative early healing in response to the interleukin-4 treatment. However, continued treatment of interleukin-4 to day 11 antagonized this early benefit and slowed healing. Together, these results suggest that interleukin-4 influences the macrophages and T-lymphocytes but also stimulates fibroblasts associated with the proliferative phase of healing in a dose-...

Stat6 activation is essential for interleukin-4 induction of P-selectin transcription in juman umbilical vein endothelial cells

Khew-Goodall, Y.; Wadham, C.; Stein, B.; Gamble, J.; Vadas, M.
Fonte: American Heart Association Publicador: American Heart Association
Tipo: Artigo de Revista Científica
Publicado em //1999 Português
Relevância na Pesquisa
65.93%
Chronic upregulation of P-selectin expression on the surface of the endothelium has been observed in and likely contributes to a number of chronic inflammatory diseases, including atherosclerosis. Agonists of P-selectin expression fall into 2 categories: those that induce a very rapid, transient increase, lasting only hours, and those that induce prolonged upregulation lasting days. It is the latter group, which includes interleukin-4 (IL-4), that is likely to be a mediator of chronic P-selectin upregulation. The increase in P-selectin expression induced by IL-4 results from increased transcriptional activation of the P-selectin gene. The aim of this study was to deduce the postreceptor signaling pathway(s) giving rise to the prolonged increase in P-selectin expression induced by IL-4. We demonstrate the existence of 2 functional signal transducer and activator of transcription 6 (Stat6) binding sites on the P-selectin promoter and further demonstrate, by functional analysis of the P-selectin promoter, that binding of activated Stat6 to at least 1 site is essential for IL-4-induction of P-selectin transcription. Site 1 (nucleotide[nt] −142) bound Stat6 with a higher affinity than did site 2 (nt −229), and this difference was reflected functionally as constructs in which only site 1 was functional showed full IL-4 inducibility...

IL-4 mediated conditioning of human dendritic cell precursors to become IL-12p70 producing DC; Humane dendritische Vorläuferzellen werden durch eine IL-4 Konditionierung zu IL-12p70 produzierenden dendritischen Zellen

Guenova, Emmanuella
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
56%
During chronic inflammation, activated dendritic cells (DC), constantly migrate from peripheral tissues to draining lymph nodes and are replaced by newly recruited DC-precursors that differentiate into tissue resident DC. It is well documented that interleukin (IL)-4 expression dominates the early phases of multiple acquired immune responses, especially inflammation in atopic diseases such as atopic dermatitis and that DC are abundant at this early stage of inflammation. However, the precise role of IL-4 during early inflammation and its impact on the differentiation of newly recruited DC precursors remained elusive. To characterize the functional impact of IL-4 on the differentiation of human DC, we investigated in detail the role of IL-4 on the differentiation of monocytes into DC. As described, IL-4 is an inevitable prerequisite for the generation of DC and concentrations between 5 and 50ng/ml induced phenotypically indistinguishable DC upon activation with LPS. However, DC populations, differentiated under higher but physiological concentrations of IL-4, revealed a distinct polarized functional phenotype. High IL-4 concentrations during DC-precursor development resulted in DC that produced large amounts of IL-12p70, low IL-10 and primed naïve CD4+ T cells to become Th1 cells. In contrast...

Reduced Interleukin-4 Receptor α Expression on CD8+ T Cells Correlates with Higher Quality Anti-Viral Immunity

Wijesundara, Danushka K.; Tscharke, David C.; Jackson, Ronald J.; Ranasinghe, Charani
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
56.03%
With the hope of understanding how interleukin (IL)-4 and IL-13 modulated quality of anti-viral CD8(+) T cells, we evaluated the expression of receptors for these cytokines following a range of viral infections (e.g. pox viruses and influenza virus). Results clearly indicated that unlike other IL-4/IL-13 receptor subunits, IL-4 receptor α (IL-4Rα) was significantly down-regulated on anti-viral CD8(+) T cells in a cognate antigen dependent manner. The infection of gene knockout mice and wild-type (WT) mice with vaccinia virus (VV) or VV expressing IL-4 confirmed that IL-4, IL-13 and signal transducer and activator of transcription 6 (STAT6) were required to increase IL-4Rα expression on CD8(+) T cells, but not interferon (IFN)-γ. STAT6 dependent elevation of IL-4Rα expression on CD8(+) T cells was a feature of poor quality anti-viral CD8(+) T cell immunity as measured by the production of IFN-γ and tumor necrosis factor α (TNF-α) in response to VV antigen stimulation in vitro. We propose that down-regulation of IL-4Rα, but not the other IL-4/IL-13 receptor subunits, is a mechanism by which CD8(+) T cells reduce responsiveness to IL-4 and IL-13. This can improve the quality of anti-viral CD8(+) T cell immunity. Our findings have important implications in understanding anti-viral CD8(+) T cell immunity and designing effective vaccines against chronic viral infections.; This work was supported by the Australian National Health and Medical Research Council project grant award 525431 (CR) and development grant award APP1000703 (CR) and the Australian Centre for Hepatitis and HIV Virology EOI grant 2010 (CR). The funders had no role in study design...

Murine filariasis: interleukin 4 and interleukin 5 lead to containment of different worm developmental stages

Volkmann, Lars; Bain, Odile; Saeftel, Michael; Specht, Sabine; Fischer, Kerstin; Brombacher, Frank; Matthaei, Klaus; Hoerauf, Achim
Fonte: Springer Publicador: Springer
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
56.03%
We compared the impact of IL-4 and IL-5 deficiency during the fully permissive infection of BALB/c mice with the rodent filaria Litomosoides sigmodontis. IL-5, in contrast to IL-4, is crucial for the containment of adult worms during short- and long-term

Interleukin-4-mediated downregulation of cytotoxic T lymphocyte activity is associated with reduced proliferation of antigen-specific CD8 + T cells

Rolph, M; Ramshaw, Ian
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
55.94%
During virus infection, exogenous IL-4 strongly downregulates expression of antiviral cytokines and cytotoxic T lymphocyte (CTL) responses. In this study, we have employed a T cell receptor (TCR) transgenic system to more closely investigate the effect of IL-4 on CTL activity. This system involves mice transgenic for an H2-Kb restricted TCR recognising an ovalbumin (OVA)-specific peptide (OT-I mice), and recombinant vaccinia viruses expressing the gene for OVA (VV-OVA), or OVA together with IL-4 (VV-OVA-IL-4). Spleen cells from OT-I mice were adoptively transferred to irradiated C57BL/6 mice infected with VV-OVA or VV-OVA-IL-4. Five days following transfer, markedly stronger CTL activity was detected in VV-OVA- than in VV-OVA-IL-4-infected recipients. The reduction in CTL activity was associated with a reduction in the number of OVA-specific CD8+ T cells. Proliferation of cells from VV-OVA-IL-4-infected recipients was dramatically reduced, and this is a likely explanation for the IL-4-mediated reduction in the total number of OVA-specific cells and the reduced cytotoxic activity. On a per cell basis, the production of IFNγ and cytotoxic activity of OVA-specific CD8+ cells was not influenced by IL-4. Taken together, our results indicate that the reduction in CTL activity by exogenous IL-4 is due to a reduced number of antigen-specific effectors...

On-column refolding of recombinant human interleukin-4 from inclusion bodies

Razeghifard, Mohammad
Fonte: Academic Press Publicador: Academic Press
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
65.93%
Interleukin-4 (IL4) is a multifunctional cytokine which plays a key role in the immune system. Several antagonists/agonists of IL4 are reported through mutagenesis studies, but their solution structural studies using nuclear magnetic resonance (NMR) spectroscopy are hindered as milligram quantities of isotopically labeled protein are required for structural refinements. In this work, a His-tagged recombinant form of human IL4 was overexpressed in Escherichia coli under the control of a T7 promoter. The resulting inclusion bodies were separated from cellular debris by centrifugation and solubilized by 6M guanidine-HCl in the presence of reducing agents. The denatured IL4 was immobilized on Ni2+-fractogel beads and refolded in a single chromatographic step by gradual removal of denaturant. This protocol yielded 15-20mg of isotope-enriched protein from 1L of culture grown in minimal medium. The refolded protein was highly pure and was correctly folded as judged by its two-dimensional NMR spectrum. To show the successful application of this refolding protocol to IL4 variants,15N-labeled Y124D-IL4 was also prepared and its first two-dimensional NMR spectrum was presented.

Combination of IFN-� and I-4 induce distinct profiles of dendritic cel-associated immunoregulatory properties

Banyer, Joanne; Halliday, Damien; Thomson, Scott; Hamilton, Nicholas H R
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
55.93%
Interferon gamma (IFN-γ) and interleukin-4 (IL-4) are not only generated during cell-mediated immunity (CMI) and humoral immunity (HI), but are also generated by innate immune cells in response to pathogenic factors. How these cytokines differentially ef