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Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria

Ururahy, Marcela Abbott Galvao; Loureiro, Melina Bezerra; Freire-Neto, Francisco Paulo; Souza, Karla Simone Costa de; Zuhl, Irina; Brandão-Neto, José; Hirata, Rosario Dominguez Crespo; Doi, Sonia de Quateli; Arrais, Ricardo Fernando; Hirata, Mario Hiroy
Fonte: WILEY-BLACKWELL; MALDEN Publicador: WILEY-BLACKWELL; MALDEN
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
55.77%
Objective: To study the activation of an inflammatory cascade through leukocyte mRNA expression of TLR2, TLR4, MyD88, and pro-inflammatory cytokines in individuals with childhood onset type 1 diabetes. Design and methods: Seventy-six type 1 diabetic patients and 100 normoglycemic subjects (NG) 6 to 20 years old were recruited. Type 1 diabetic patients (DM1) were considered to have good (DM1G) or poor (DM1P) glycemic control according to the values of glycated hemoglobin. TLR2, TLR4, MyD88, interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) mRNA expressions were measured in peripheral blood leukocytes (PBL) by real-time polymerase chain reaction (PCR). Urea, creatinine, albumin, and total protein serum levels were determined. Urinary albumin-to-creatinine ratio (ACR) was calculated. Results: DM1 and DM1P patients showed higher glycated hemoglobin (10 and 11%, respectively) and serum glucose concentrations (208 and 226 mg/ dL, respectively) compared to NG (Glycated hemoglobin: 7% and glucose: 76 mg/ dL) (p < 0.05). PBL mRNA expressions of TLR2, MyD88, IL-1 beta, IL-6, and TNF-alpha were higher in DM1 and TLR2, IL-1 beta, and IL-6 expressions were higher in DMP1 compared to NG (p < 0.05). In DM1, serum albumin and total protein were lower...

Silibinin modulates the NF-kappa b pathway and pro-inflammatory cytokine production by mononuclear cells from preeclamptic women

Innocenti Giorgi, Vanessa S.; Peracoli, Maria Terezinha S.; Peraçoli, José Carlos; Witkin, Steven S.; Bannwart-Castro, Camila F.
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 67-72
Português
Relevância na Pesquisa
55.78%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Processo FAPESP: 10/00776-0; Preeclampsia (PE) is a complication of human pregnancy associated with an intense inflammatory response involving leukocyte activation, as well as elevated production of pro-inflammatory cytokines. The nuclear transcription factor-kappa B (NF-kappa B) is present in cells of the immune system and is responsible for transcription of genes coding for pro-inflammatory proteins. Silibinin is the main component of silymarin, a polyphenolic extract obtained from fruits and seeds of Silybum marianum with potent hepatoprotective and anti-inflammatory activities. In this study, we assessed whether silibinin modulated NF-kappa B activity and the production of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMCs) from preeclamptic patients. PBMC from women with PE, normotensive (NT) pregnant women, and nonpregnant (NP) women were cultured with or without silibinin (5 mu M and 50 mu M) and 1 mu g/mL lipopolysaccharide (LPS) for 18 h. The supernatants were assayed for tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) by ELISA. Cells were cultured for 30 min to evaluate NF-kappa B activity. There was increased endogenous activation of NF-kappa B as well as TNF-alpha and IL-1 beta release by PBMC in the PE group compared with the NT and NP groups. A positive correlation between NF-kappa B activity and cytokine production was also observed in the PE group. Silibinin was capable of reducing...

Intraarticular expression of biologically active interleukin 1-receptor-antagonist protein by ex vivo gene transfer.

Bandara, G; Mueller, G M; Galea-Lauri, J; Tindal, M H; Georgescu, H I; Suchanek, M K; Hung, G L; Glorioso, J C; Robbins, P D; Evans, C H
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/11/1993 Português
Relevância na Pesquisa
55.78%
Gene therapy offers a radical different approach to the treatment of arthritis. Here we have demonstrated that two marker genes (lacZ and neo) and cDNA coding for a potentially therapeutic protein (human interleukin 1-receptor-antagonist protein; IRAP or IL-1ra) can be delivered, by ex vivo techniques, to the synovial lining of joints; intraarticular expression of IRAP inhibited intraarticular responses to interleukin 1. To achieve this, lapine synoviocytes were first transduced in culture by retroviral infection. The genetically modified synovial cells were then transplanted by intraarticular injection into the knee joints of rabbits, where they efficiently colonized the synovium. Assay of joint lavages confirmed the in vivo expression of biologically active human IRAP. With allografted cells, IRAP expression was lost by 12 days after transfer. In contrast, autografted synoviocytes continued to express IRAP for approximately 5 weeks. Knee joints expressing human IRAP were protected from the leukocytosis that otherwise follows the intraarticular injection of recombinant human interleukin 1 beta. Thus, we report the intraarticular expression and activity of a potentially therapeutic protein by gene-transfer technology; these experiments demonstrate the feasibility of treating arthritis and other joint disorders with gene therapy.

Tyrosine kinase inhibitor suppresses coronary arteriosclerotic changes and vasospastic responses induced by chronic treatment with interleukin-1 beta in pigs in vivo.

Ito, A; Shimokawa, H; Kadokami, T; Fukumoto, Y; Owada, M K; Shiraishi, T; Nakaike, R; Takayanagi, T; Egashira, K; Takeshita, A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1995 Português
Relevância na Pesquisa
55.79%
We recently demonstrated that chronic treatment with IL-1 beta induces coronary arteriosclerotic changes and vasospastic responses to autacoids in pigs in vivo and that those responses are importantly mediated by PDGF. The receptors for PDGF and other major growth factors are known to have tyrosine kinase activity. We therefore investigated the effects of a selective tyrosine kinase inhibitor, ST 638, on those responses induced by IL-1 beta in our swine model. Intimal thickening and coronary vasospastic responses to serotonin and histamine were induced at the site of the coronary artery where IL-1 beta was chronically and locally applied. These responses were significantly suppressed in a dose-dependent manner by cotreatment with ST 638. In addition, ST 494, which is an inactive form of ST 638, did not inhibit those responses. The treatment with ST 638 alone did not affect the coronary vasoconstricting responses to the autacoids. Immunoblotting using an antibody to phosphotyrosines confirmed the inhibitory effects of ST 638 on the tyrosine phosphorylations induced by IL-1 beta. These results thus suggest that tyrosine kinase activation may play an important role in mediating the effects of IL-1 beta, while also suggesting that ST 638 has an inhibitory effect on the arteriosclerotic changes and vasospastic responses to autacoids in our swine model in vivo.

Inhibition of in vitro erythropoiesis by soluble mediators in Plasmodium chabaudi AS malaria: lack of a major role for interleukin 1, tumor necrosis factor alpha, and gamma interferon.

Yap, G S; Stevenson, M M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1994 Português
Relevância na Pesquisa
55.78%
By using erythropoietin-dependent proliferation of splenic erythroid cells as an in vitro erythropoiesis model system, we demonstrate that spleen cells from Plasmodium chabaudi AS-infected C57BL/6 mice potently inhibited erythroid cell proliferation. Inhibitory activity was detected in spleen cell conditioned media (SPCM) prepared from infected mice but not from uninfected mice. The inhibitory activity in SPCM was characterized as being heat sensitive, macromolecular, and host derived. The inhibitory activity was not reversed by increasing the erythropoietin concentration and was found to be specific for the late erythroid lineage. Mouse strains, which differ in their resistance to P. chabaudi AS infection, produced and responded to the inhibitory activity to a similar extent. Putative immune mediators, interleukin 1 alpha, interleukin 1 beta, and gamma interferon, were found to be potent inhibitors of erythroid cell proliferation. However, antibody neutralization experiments failed to demonstrate a major role for these cytokines in the inhibitory activity of SPCM. Our results suggest that the elaboration of inhibitor(s) of erythropoiesis in hemopoietic organs of Plasmodium-infected mice may impair erythroid regeneration. The identity of the inhibitory mediator(s) is presently unknown but is distinct from interleukin 1...

Lactoferrin release and interleukin-1, interleukin-6, and tumor necrosis factor production by human polymorphonuclear cells stimulated by various lipopolysaccharides: relationship to growth inhibition of Candida albicans.

Palma, C; Cassone, A; Serbousek, D; Pearson, C A; Djeu, J Y
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1992 Português
Relevância na Pesquisa
55.78%
Lipopolysaccharides (LPSs) from Escherichia coli, Serratia marcescens, and Salmonella typhimurium, at doses from 1 to 100 ng/ml, strongly enhanced growth inhibition of Candida albicans by human polymorphonuclear leukocytes (PMN) in vitro. Flow cytometry analysis demonstrated that LPS markedly augmented phagocytosis of Candida cells by increasing the number of yeasts ingested per neutrophil as well as the number of neutrophils capable of ingesting fungal cells. LPS activation caused augmented release of lactoferrin, an iron-binding protein which itself could inhibit the growth of C. albicans in vitro. Antibodies against lactoferrin effectively and specifically reduced the anti-C. albicans activity of both LPS-stimulated and unstimulated PMN. Northern (RNA blot) analysis showed enhanced production of mRNAs for interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 and in neutrophils within 1 h of stimulation with LPS. The cytokines were also detected in the supernatant of the activated PMN, and their synthesis was prevented by pretreatment of LPS-stimulated PMN with protein synthesis inhibitors, such as emetine and cycloheximide. These inhibitors, however, did not block either lactoferrin release or the anti-Candida activity of LPS-stimulated PMN. These results demonstrate the ability of various bacterial LPSs to augment neutrophil function against C. albicans and suggest that the release of a candidastatic...

Shiga toxin-associated hemolytic-uremic syndrome: combined cytotoxic effects of Shiga toxin, interleukin-1 beta, and tumor necrosis factor alpha on human vascular endothelial cells in vitro.

Louise, C B; Obrig, T G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1991 Português
Relevância na Pesquisa
55.78%
This study explores the relationship between Shiga toxin-producing Shigella or Escherichia coli strains and the development of vascular complications in humans following bacillary dysentery. We propose that endotoxin-elicited interleukin-1 or tumor necrosis factor alpha (TNF) may combine with Shiga toxin to facilitate vascular damage characteristic of hemolytic-uremic syndrome. This study examines the cytotoxic effects of Shiga toxin, interleukin-1, and TNF on cultured human umbilical vein endothelial cells (HUVEC). Both Shiga toxin and TNF were cytotoxic to HUVEC, although HUVEC obtained from individual umbilical cords differed in their sensitivities to these agents. With Shiga toxin-sensitive HUVEC, combinations of TNF with Shiga toxin resulted in a synergistic cytotoxic effect. In contrast, interleukin-1 was not cytotoxic to HUVEC, nor did it enhance cell death in combination with Shiga toxin. The synergistic cytotoxic response of HUVEC to Shiga toxin and TNF was dose and time dependent for both agents and could be neutralized by monoclonal antibodies directed against either Shiga toxin or TNF. This synergistic response was delayed, being maximal on day 2. Preincubation (24 h) of HUVEC with TNF sensitized the cells to Shiga toxin. TNF alone had no effect on HUVEC protein synthesis but enhanced the inhibitory activity of Shiga toxin. These results are consistent with a role for Shiga toxin in the development of hemolytic-uremic syndrome at the level of the vascular endothelium in humans.

Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues. Effects of interleukin-1 beta, phorbol ester, and corticosteroids.

Crofford, L J; Wilder, R L; Ristimäki, A P; Sano, H; Remmers, E F; Epps, H R; Hla, T
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1994 Português
Relevância na Pesquisa
55.79%
High levels of immunoreactive cyclooxygenase (Cox; prostaglandin H synthase) are present in synovia from patients with rheumatoid arthritis (RA). We now show that the recently identified inducible isoform of Cox, Cox-2, is expressed in synovia from patients with RA. To further explore modulation of the Cox isoforms in RA synovial tissues, we examined the expression and modulation of Cox-1 and -2 in rheumatoid synovial explant cultures and cultured rheumatoid synovial fibroblast-like cells (synoviocytes). Immunoprecipitation of in vitro labeled proteins and Western blot analysis demonstrated the presence of both Cox-1 and -2 under basal conditions in freshly explanted rheumatoid synovial tissues. De novo synthesis of Cox-2 polypeptide was enhanced by IL-1 beta or PMA, and dramatically suppressed by dexamethasone (dex). Cox-1 expression, under the same conditions, showed only minor variation. Since mRNA for Cox-2 is highly unstable, we examined the regulation of Cox-2 transcripts in cultured rheumatoid synoviocytes. Under basal conditions both Cox-1 and -2 mRNAs were present at low levels, but Cox-2 mRNA was markedly increased by treatment with IL-1 beta or PMA. dex markedly suppressed the induction of Cox-2 mRNA. In sharp contrast, Cox-1 transcripts were not modulated by IL-1 beta or dex. These data suggest that modulation of Cox-2 expression by IL-1 beta and corticosteroids may be an important component of the inflammatory process in synovial tissues from patients with RA.

Amplification of nitric oxide synthase expression by nitric oxide in interleukin 1 beta-stimulated rat mesangial cells.

Mühl, H; Pfeilschifter, J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1995 Português
Relevância na Pesquisa
55.79%
Nitric oxide (NO) plays an important role in immunological reactions as a host defense mechanism against tumor cells and invasive microorganisms, but it may also damage healthy tissue. The excessive formation of NO in IL-1 beta-stimulated renal mesangial cells not only alters glomerular filtration, but it may also cause tissue injury and thus contribute to the pathogenesis of certain forms of glomerulonephritis. We report here that, although NO alone has no evident effect on NO synthase expression, it potently augments IL-1 beta-stimulated NO synthase expression in mesangial cells. NO donors such as sodium nitroprusside and S-nitroso-N-acetyl-D,L-penicillamine markedly increase IL-1 beta-induced NO synthase mRNA and protein levels as well as enzyme activity. Nuclear run-on experiments suggest that NO acts to increase IL-1 beta-induced NO synthase gene expression at the transcriptional level. Furthermore, inhibition of NO synthesis by different pharmacological approaches reduces IL-1 beta-induced NO synthase expression, thus suggesting that NO functions in a positive feedback loop that speeds up and strengthens its own biosynthesis. We suggest that this potent amplification mechanism forms the basis for the excessive formation of NO in acute and chronic inflammatory diseases.

Increases in levels of procollagenase messenger RNA in cultured fibroblasts induced by human recombinant interleukin 1 beta or serum follow c-jun expression and are dependent on new protein synthesis.

Conca, W; Kaplan, P B; Krane, S M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1989 Português
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55.79%
The protein encoded by the protooncogene c-jun, included in the activator protein-1 (AP-1) complex, is probably the critical trans-acting factor controlling transcription of the procollagenase gene which is rate limiting for subsequent synthesis of procollagenase. Therefore, to elucidate possible mechanisms whereby IL-1 stimulates procollagenase synthesis, we measured levels of c-jun and procollagenase mRNA in human serum-starved dermal fibroblasts in response to human recombinant IL-1 beta (hrIL-1 beta). hrIL-1 beta or serum induced rapid increases in c-jun mRNA levels; mRNA levels declined rapidly after hrIL-1 beta and more slowly after exposure to serum. The increases in levels of c-jun mRNA preceded the increases in procollagenase mRNA. Whereas the increases in levels of procollagenase mRNA were blunted by cycloheximide, those of c-jun mRNA were enhanced. We interpret these results as follows: IL-1 or serum induce transcription of c-jun by mechanisms independent of new protein synthesis; c-JUN, the protein product of c-jun in the AP-1 complex, is an essential mediator of the effects of IL-1 or serum in the subsequent induction of expression of the procollagenase gene.

Participation of the cytokines interleukin 6, tumor necrosis factor-alpha, and interleukin 1-beta secreted by acute myelogenous leukemia blasts in autocrine and paracrine leukemia growth control.

Oster, W; Cicco, N A; Klein, H; Hirano, T; Kishimoto, T; Lindemann, A; Mertelsmann, R H; Herrmann, F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1989 Português
Relevância na Pesquisa
55.78%
Autonomous in vitro growth of myeloid leukemic colony-forming cells may in part result from autocrine production of colony-stimulating factors (CSF). Some acute myeloid leukemia (AML) samples, however, fail to synthesize CSF despite growing autonomously in agar, and are therefore believed to bypass CSF requirements. Cytokines such as IL-6, tumor necrosis factor (TNF)-alpha, and IL-1, products of cells of the myeloid lineage, are known to be involved in growth control of myeloid progenitor cells. Since these molecules may also contribute to autocrine and paracrine growth regulation of myeloid leukemias, we screened a series of AML for cytokine production. In addition, possible roles of IL-6, TNF-alpha, and IL-1 in growth control of AML were investigated in vitro. We show that a substantial proportion of AML cells produce IL-6, TNF-alpha, and IL-1-beta and use these mediators to stimulate their growth by disparate mechanisms: IL-6 acts as a costimulator to enhance CSF-induced clonogenicity of AML blasts. TNF-alpha induces CSF production by endothelial cells and may therefore provide a paracrine loop to support leukemia growth.

Influence of interleukin 1 beta on tenascin distribution in human normal and osteoarthritic cartilage: a quantitative immunohistochemical study.

Chevalier, X; Claudepierre, P; Groult, N; Godeau, G J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1996 Português
Relevância na Pesquisa
55.78%
OBJECTIVE: To determine the influence of IL-1 beta on the presence and the distribution of tenascin in matrix of human normal and osteoarthritic cartilage explants. METHODS: Cartilage was grown in organotypic culture with or without IL-1 beta (10 ng ml1). Tenascin antigen was detected on cryopreserved cartilage sections by immunohistochemical techniques with a monoclonal antibody directed against all tenascin isoforms (BC-4), and then quantified by video imaging densitometry. RESULTS: Tenascin was present in normal cartilage explants and increased in osteoarthritic cartilage explants. Treatment of normal and osteoarthritic cartilage explants with IL-1 beta (10 ng ml-1) induced an increase in tenascin content, which was particularly high in normal cartilage and predominated in the superficial layers of damaged cartilage. There was no obvious correlation between proteoglycan loss and presence of tenascin. CONCLUSIONS: In human normal and osteoarthritic cartilage explants, the presence and the distribution of tenascin are influenced by IL-1 beta.

Spontaneous and LPS-stimulated production of intracellular IL-1 beta by synovial macrophages in rheumatoid arthritis is inhibited by IFN-gamma.

Ruschen, S; Lemm, G; Warnatz, H
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1989 Português
Relevância na Pesquisa
55.78%
In the peripheral blood (PB) as well as the synovial fluid (SF) of rheumatoid arthritis (RA) patients significantly elevated levels of interleukin 1 beta (IL-1 beta) were determined compared to controls by means of a sensitive and specific ELISA (median values: 280 pg/ml and 325 pg/ml vs. less than 20 pg/ml). In 12-h cell cultures of adherent cells, significantly increased spontaneous intracellular IL-1 beta production was determined in SF macrophage (SFM phi) cultures of RA patients compared to PB monocyte (PBMo) cultures of controls (median values: 91.0 ng/10(6) cells vs. 31.5 ng/10(6) cells). However, secretion must be elicited by additional stimulation with lipopolysaccharide (LPS). Interferon-gamma (IFN-gamma) significantly inhibited the spontaneous intracellular IL-1 beta production in SFM phi 12-h cultures of RA patients.

Interferon-gamma modulates messenger RNA levels of c-sis (PDGF-B chain), PDGF-A chain, and IL-1 beta genes in human vascular endothelial cells.

Suzuki, H.; Shibano, K.; Okane, M.; Kono, I.; Matsui, Y.; Yamane, K.; Kashiwagi, H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1989 Português
Relevância na Pesquisa
55.79%
The authors have investigated the effects of cytokines and lipopolysaccharide (LPS) on mRNA levels of c-sis (platelet-derived growth factor (PDGF)-B chain), PDGF-A chain, and interleukin 1 beta (IL-1 beta) genes in human vascular endothelial cells (EC). IL-1, tumor necrosis factor (TNF), and LPS not only enhanced the accumulation of c-sis mRNA, but also induced IL-1 beta gene expression. Interferon-gamma (IFN-gamma), in contrast, suppressed the accumulation of c-sis mRNA profoundly and PDGF-A chain mRNA to a lesser extent. The cytokine, in addition, suppressed the release of PDGF-like proteins by EC, while maintaining the growth of EC. IFN-gamma, however, augmented the levels of IL-1 beta mRNA in cultured EC in association with LPS or IL-1, suggesting that the suppression of c-sis expression was not mediated through modulation of IL-1 gene expression by IFN-gamma. These results raise the possibility that IFN-gamma may play a novel regulatory role in the pathogenesis of vascular diseases such as atherosclerosis and vasculitis.

Regional and cellular codistribution of interleukin 1 beta and nerve growth factor mRNA in the adult rat brain: possible relationship to the regulation of nerve growth factor synthesis

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/10/1990 Português
Relevância na Pesquisa
55.79%
We have found a regional distribution of IL 1 beta mRNA and IL 1 activity in the normal adult rat brain, which reveals at least partially a colocalization with nerve growth factor (NGF). The predominantly neuronal signal patterns were found over the granule cells of the dentate gyrus, the pyramidal cells of the hippocampus, the granule cells of the cerebellum, the granule and periglomerular cells of the olfactory bulb, and over dispersed cells of the ventromedial hypothalamus and of the frontal cortex. In these areas also the highest levels of IL 1 activity were observed. In the striatum and septum much lower levels of IL 1 beta mRNA and IL 1 activity (shown for the striatum), most likely synthesized by glial cells, could be determined. IL 1 beta-expressing cells were mainly found in brain regions that also synthesize NGF mRNA as shown by in situ hybridization. NGF mRNA could be demonstrated over pyramidal cells of the hippocampus, granule cells of the dentate gyrus, periglomerular cells of the olfactory bulb and over prefrontal cortex neurons. These data indicate that IL 1 beta, among other factors, might also play a regulatory role in the synthesis of NGF in the CNS, as has been demonstrated in the peripheral nervous system (Lindholm...

Autocrine stimulation of interleukin 1 beta in acute myelogenous leukemia cells

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/11/1987 Português
Relevância na Pesquisa
55.79%
A significant increase in CD25 antigen-positive cells by IL-1 was observed in cells of a patient with M7 acute myelogenous leukemia. Basal proliferation and expression of CD25 antigen by the M7 leukemic cells were inhibited by addition of anti-IL-1 beta antibody in a dose- dependent manner, but not by rabbit anti-IL-1 alpha antibody. Culture supernatants of these leukemic cells contained IL-1 activity, which was specifically inhibited by addition of anti-IL-1 beta antibody, and Northern blot analysis detected intracellular IL-1 beta mRNA. These results indicated that autocrine secretion of IL-1 beta was involved in proliferation of some myelogenous leukemic cells.

Repeat tuberculin skin testing leads to desensitisation in naturally infected tuberculous cattle which is associated with elevated interleukin-10 and decreased interleukin-1 beta responses

Coad, Michael; Clifford, Derek; Rhodes, Shelley G.; Hewinson, R. Glyn; Vordermeier, H. Martin; Whelan, Adam O.
Fonte: EDP Sciences Publicador: EDP Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
55.78%
The principal surveillance tool used to control bovine tuberculosis in cattle is the removal of animals that provide a positive response to the tuberculin skin-test. In this study we performed a longitudinal investigation of the immunological and diagnostic consequences of repeated short-interval skin-tests in cattle naturally infected with Mycobacterium bovis. Tuberculin skin-test positive cattle were subjected to up to four further intradermal comparative cervical skin-tests at approximately 60-day intervals. A significant progressive reduction in the strength of the skin-test was observed after successive tests. In contrast, the magnitude of interferon-γ (IFN-γ) responses was not influenced by repeat skin-testing either transiently around the time of each skin-test or longitudinally following repeated tests. A significant boost in blood interleukin-10 (IL-10) production was observed within 3 days following each skin-test although the magnitude of this boosted response returned to lower levels by day 10 post-test. The application of a novel multiplex assay to simultaneously measure seven cytokines and chemokines also identified that skin-testing resulted in a significant and progressive reduction in antigen specific interleukin-1β (IL-1β) whilst confirming stable IFN-γ and elevated IL-10 responses in the blood. Therefore...

Roles of Inflammatory Caspases during Processing of Zebrafish Interleukin-1β in Francisella noatunensis Infection

Vojtech, Lucia N.; Scharping, Nicole; Woodson, James C.; Hansen, John D.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /08/2012 Português
Relevância na Pesquisa
55.78%
The interleukin-1 family of cytokines are essential for the control of pathogenic microbes but are also responsible for devastating autoimmune pathologies. Consequently, tight regulation of inflammatory processes is essential for maintaining homeostasis. In mammals, interleukin-1 beta (IL-1β) is primarily regulated at two levels, transcription and processing. The main pathway for processing IL-1β is the inflammasome, a multiprotein complex that forms in the cytosol and which results in the activation of inflammatory caspase (caspase 1) and the subsequent cleavage and secretion of active IL-1β. Although zebrafish encode orthologs of IL-1β and inflammatory caspases, the processing of IL-1β by activated caspase(s) has never been examined. Here, we demonstrate that in response to infection with the fish-specific bacterial pathogen Francisella noatunensis, primary leukocytes from adult zebrafish display caspase-1-like activity that results in IL-1β processing. Addition of caspase 1 or pancaspase inhibitors considerably abrogates IL-1β processing. As in mammals, this processing event is concurrent with the secretion of cleaved IL-1β into the culture medium. Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase A and caspase B...

Gemfibrozil, a lipid-lowering drug, upregulates interleukin-1 receptor antagonist in mouse cortical neurons: Implications for neuronal self-defense

Corbett, Grant T.; Roy, Avik; Pahan, Kalipada
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
55.8%
Chronic inflammation is becoming a hallmark of several neurodegenerative disorders and accordingly, interleukin-1 beta (IL-1β), a proinflammatory cytokine, is implicated in the pathogenesis of neurodegenerative diseases. While IL-1β binds to its high-affinity receptor, interleukin-1 receptor (IL-1R), and upregulates proinflammatory signaling pathways, interleukin-1 receptor antagonist (IL-1Ra) adheres to the same receptor and inhibits proinflammatory cell signaling. Therefore, upregulation of IL-1Ra is considered important in attenuating inflammation. The present study underlines a novel application of gemfibrozil, an FDA-approved lipid-lowering drug, in increasing the expression of IL-1Ra in primary mouse and human neurons. Gemfibrozil alone induced an early and pronounced increase in the expression of IL-1Ra in primary mouse cortical neurons. Activation of type IA p110α phosphatidylinositol 3-kinase (PI3-K) and Akt by gemfibrozil and abrogation of gemfibrozil-induced upregulation of IL-1Ra by inhibitors of PI3-K and Akt indicate a role of the PI3-K – Akt pathway in the upregulation of IL-1Ra. Gemfibrozil also induced the activation of cAMP response element-binding (CREB) via the PI3-K – Akt pathway and siRNA attenuation of CREB abolished the gemfibrozil-mediated increase in IL-1Ra. Furthermore...

Differential induction of nitric oxide synthase in various organs of the mouse during endotoxaemia: role of TNF-alpha and IL-1-beta.

Cunha, F Q; Assreuy, J; Moss, D W; Rees, D; Leal, L M; Moncada, S; Carrier, M; O'Donnell, C A; Liew, F Y
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1994 Português
Relevância na Pesquisa
55.78%
BALB/c mice injected intraperitoneally with bacterial lipopolysaccharide (LPS) developed lethal septic shock. This was accompanied by significantly elevated concentrations of nitrite and nitrate in the plasma and expression of high levels of nitric oxide (NO) synthase activity in the lungs, heart, spleen and peritoneal macrophages. Mice pretreated with anti-tumour necrosis factor-alpha (TNF-alpha) monoclonal antibody or anti-interleukin-1 beta (IL-1 beta) polyclonal antibody were protected, in a dose-dependent manner, from endotoxin-induced mortality. This effect was accompanied by a significant reduction in plasma levels of nitrite and nitrate. Antibody treatment also reduced the level of NO synthase activity in peritoneal macrophages, spleen and heart but had no effect on enzyme expression in the lung. These results demonstrate that TNF-alpha and IL-1 beta play an important role in the induction of NO following administration of LPS and in the development of endotoxin-induced shock. In addition, NO synthase activity is differentially expressed in various organs and this may not always require TNF-alpha and IL-1 beta.