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Inflammatory Molecules (inflammatory + molecule)
Selected AbstractsHistamine induces Toll-like receptor 2 and 4 expression in endothelial cells and enhances sensitivity to Gram-positive and Gram-negative bacterial cell wall componentsIMMUNOLOGY, Issue 2 2004Jaya Talreja Summary Histamine is a major inflammatory molecule released from the mast cell, and is known to activate endothelial cells. However, its ability to modulate endothelial responses to bacterial products has not been evaluated. In this study we determined the ability of histamine to modulate inflammatory responses of endothelial cells to Gram-negative and Gram-positive bacterial cell wall components and assessed the role of Toll-like receptors (TLR) 2 and 4 in the co-operation between histamine and bacterial pathogens. Human umbilical vein endothelial cells (HUVEC) were incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or peptidoglycan (PGN) in the presence or absence of histamine, and the expression and release of interleukin-6 (IL-6), and NF-,B translocation were determined. The effect of histamine on the expression of mRNA and proteins for TLR2 and TLR4 was also evaluated. Incubation of HUVEC with LPS, LTA and PGN resulted in marked enhancement of IL-6 mRNA expression and IL-6 secretion. Histamine alone markedly enhanced IL-6 mRNA expression in HUVEC, but it did not stimulate proportional IL-6 release. When HUVEC were incubated with LPS, LTA, or PGN in the presence of histamine marked amplification of both IL-6 production and mRNA expression was noted. HUVEC constitutively expressed TLR2 and TLR4 mRNA and proteins, and these were further enhanced by histamine. The expression of mRNAs encoding MD-2 and MyD88, the accessory molecules associated with TLR signalling, were unchanged by histamine treatment. These results demonstrate that histamine up-regulates the expression of TLR2 and TLR4 and amplifies endothelial cell inflammatory responses to Gram-negative and Gram-positive bacterial components. [source] Expression of inflammatory molecules and associations with BMI in childrenEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2010George V. Z. Dedoussis Eur J Clin Invest 2010; 40 (5): 388,392 Abstract Background, Adipose tissue secrets several adipokines that have been proposed to be enrolled in many inflammatory pathways. Our aim was to investigate the adipokine expression in adipose tissue and peripheral blood mononuclear cells (PBMCs) in children. Materials and methods, Thirty-one (17 males and 14 females) healthy children aged 10·9 ± 1·8 years with a body mass index (BMI) of 19·3 ± 3·5 kg m,2 were enrolled. Adipokines (TNF-alpha, IL-6 and leptin) gene expression was quantified by real-time quantitative PCR in adipose tissue and PBMCs from the same children. Their serum levels were also measured. Results, BMI was positively correlated with leptin gene expression in adipose tissue and with leptin serum levels (, = 0·476, P = 0·006 and , = 0·576, P = 0·003 respectively). Leptin's serum levels were positively correlated with leptin gene expression in adipose tissue (, = 0·462, P = 0·02). Adipose tissue gene expression of leptin and TNF-alpha and serum leptin and TNF-alpha serum levels were positively correlated (, = 0·752, P < 0·001, , = 0·311 and P = 0·015 respectively). In PBMCs, a positive correlation between TNF-alpha and IL-6 expression was found (, = 0·526, P = 0·042). Conclusion, We demonstrated powerful correlations of adipokines gene expression in adipose tissue and PBMCs in children, underlying that these molecules share common pathways related to childhood obesity. [source] Myeloid-derived suppressor cells in inflammation: Uncovering cell subsets with enhanced immunosuppressive functionsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2009Vincenzo Bronte Abstract Although originally described in tumor-bearing hosts, myeloid-derived suppressor cells (MDSC) have been detected under numerous pathological situations that cause enhanced demand of myeloid cells. Thus, MDSC might be part of a conserved response to different endogenous and exogenous stress signals, including inflammation. Two processes are fundamental for MDSC biology: differentiation from myeloid progenitors and full activation of their immune regulatory program by factors released from activated T cells or present in the microenvironment conditioned by either tumor growth or inflammation. How these two processes are controlled and linked is still an open question. In this issue of the European Journal of Immunology, a paper demonstrates that a combination of the known inflammatory molecules, IFN-, and LPS, sustains MDSC expansion and activation while suppressing differentiation of DC from bone marrow precursors. Moreover, this paper contributes to defining the cell subsets that possess immunoregulatory properties within the broad population of CD11b+Gr-1+ cells, often altogether referred to as MDSC. [source] Triclosan inhibition of acute and chronic inflammatory gene pathwaysJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2010Silvana P. Barros Barros SP, Wirojchanasak S, Barrow DA, Panagakos F, Devizio W, Offenbacher S. Triclosan inhibition of acute and chronic inflammatory gene pathways. J Clin Periodontol 2010; 37: 412,418. doi: 10.1111/j.1600-051X.2010.01548.x. Abstract Aim: We sought to determine whether triclosan (2,4,4,-trichloro-2,-hydroxydiphenylether), an extensively used anti-plaque agent with broad-spectrum anti-microbial activity, with reported anti-inflammatory effects via inhibition of prostaglandin E2 and interleukin 1 (IL-1),, could also more broadly suppress multiple inflammatory gene pathways responsible for the pathogenesis of gingivitis and periodontitis. Materials and Methods: As an exploratory study, the effects of triclosan on the inflammatory gene expression profile were assessed ex vivo using peripheral whole blood samples from eight periodontally healthy donors. Ten-millilitres whole blood aliquots were incubated 2 h with 0.3 ,g/ml Escherichia coli lipopolysaccharide (LPS) with or without 0.5 ,g/ml triclosan. Affymetrix microarray gene expression profiles from isolated leucocytes and pathway-specific quantitative polymerase chain reaction arrays were used to investigate changes in expression of target cytokines and cell signalling molecules. Results: Ex vivo human whole blood assays indicated that triclosan significantly down-regulated the LPS-stimulated expression of Toll-like receptor signalling molecules and other multiple inflammatory molecules including IL-1 and IL-6 and the dampening of signals that activate the T-helper type 1 acquired immune response via suppression of CD70 with concomitant up-regulation of growth factors related to bone morphogenetic protein (BMP)2 and BMP6 synthesis. Conclusions: Anti-inflammatory effects were found in this exploratory survey, including suppression of microbial-pathogen recognition pathway molecules and the suppression of acute and chronic mediators of inflammation. [source] Pro-inflammatory genetic profiles in subjects with peripheral arterial occlusive disease and critical limb ischemiaJOURNAL OF INTERNAL MEDICINE, Issue 1 2007A. Flex Abstract. Objectives., Single nucleotide polymorphisms in genes encoding inflammatory molecules may determine genetic profiles associated with increased risk of development and progression of cardiovascular diseases. In this study, we evaluated distribution and reciprocal interaction of a set of functionally important polymorphisms of genes encoding prototypical inflammatory molecules in subjects with peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI). We also investigated whether synergistic interactions between these pro-inflammatory gene polymorphisms influence the risk of PAOD and CLI. Design, subjects and methods., In a genetic association study that included 157 PAOD patients and 206 controls, the following gene polymorphisms were analysed: C-reactive protein (CRP) 1059 G/C, interleukin-6 (IL-6)-174 G/C, macrophage migration inhibitory factor (MIF)-173 G/C, monocyte chemoattractant protein (MCP-1) , 2518 A/G, E-selectin (E-Sel) Ser128Arg, intercellular adhesion molecule-1 (ICAM-1) 469 E/K, matrix metalloproteinase (MMP),1 -1607 1G/2G, MMP-3 -1171 5A/6A and MMP-9 -1563 C/T. Results:, We found that IL-6, E-sel, ICAM-1, MCP-1, MMP-1 and MMP-3 gene polymorphisms were significantly and independently associated with PAOD. We also found that these pro-inflammatory polymorphisms determine genetic profiles that are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes concomitantly carried by a given individual. Conclusions:, Pro-inflammatory genetic profiles are significantly more common in subjects with PAOD. Synergistic effects between pro-inflammatory genotypes might be potential markers for the presence and severity of atherosclerotic disorders. [source] Loss of dopaminergic neurons by the induction of inducible nitric oxide synthase and cyclooxygenase-2 via CD40: Relevance to Parkinson's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005Tatsusada Okuno Abstract A glial reaction associated with up-regulation of inflammatory molecules has been suggested to play an important role in dopaminergic neuron loss in Parkinson's disease (PD). Among inflammatory molecules, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have been focused upon as key factors in the pathogenesis. However, the mechanism of how these molecules are induced in PD brains is not clearly understood. We focused on CD40, which is expressed on neural cells and could be implicated in the neuroinflammation by inducing inflammatory molecules. We showed that both iNOS and COX-2 were up-regulated in microglia and astrocytes by CD40 stimulation in association with a low dose of interferon-, (IFN-,) in vitro. Selective loss of dopaminergic neurons was induced by costimulation with CD40 and IFN-, in mesencephalic cultures, which was protected by selective inhibitors of iNOS and/or COX-2. We also found in CD40-stimulated astrocytes an increase of a low-affinity IgE receptor CD23, which is known to induce iNOS expression. Together these data suggest that up-regulated iNOS and COX-2 via the CD40 pathway may lead to dopaminergic neuron loss and may participate in the neuroinflammaory pathway of PD. © 2005 Wiley-Liss, Inc. [source] Cytokines, implantation and early abortion: re-examining the Th1/Th2 paradigm leads to question the single pathway, single therapy conceptAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2003Gérard Chaouat Problem: Human in vitro fertilization (IVF) embryo transfer is accompanied by a low implantation rate even after a very successful IVF, and there are a certain number of ,idiopathic sterilities' which are due to repeated implantation failures. In the very same vein, the question of improving implantation rates is of prime importance in agricultural research to improve the management of livestock. Pre-implantation prenatal diagnosis cannot be accomplished in individuals who have a high rate of implantation failure, whether women undergoing IVF, or animals, during genetic cloning. Implantation cytokine networks need to be known in such a perspective. Methods: We review the evolution and theories in reproductive immunology, briefly deal with the complexity of implantation as a step by step developmental event, and then present some of our recent data in mice and human. Conclusions: We conclude that the T helper cell type 1/2 (Th1/Th2) paradigm, as useful as it has been to explain pregnancy, is no longer sufficient in view of the emerging complexity of the cytokine network at the materno-fetal interface. This is peculiarly true for implantation, which, as a step by step developmentally regulated process, involving inflammatory molecules, cannot fit into such a scheme. [source] Molecular Correlates of Scarring in Kidney Transplants: The Emergence of Mast Cell TranscriptsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009M. Mengel In the Banff consensus, infiltrates in areas of scarring are ignored. This study aimed to characterize the molecular correlates and clinical significance of scarring and inflammation in scarred areas. We assessed the extent of interstitial infiltrates, tubulitis and scarring in 129 clinically indicated renal allograft biopsies, and correlated the results with microarray expression data and allograft survival. Findings were validated in 50 additional biopsies. Transplants with scarring had a worse prognosis if the scarred area showed infiltrates. Infiltration in unscarred and scarred areas was associated with reduced death censored graft survival. In microarray analysis, infiltration in unscarred areas strongly (>r ± 0.4) correlated with 484 transcripts associated with cytotoxic T cells, interferon-gamma, macrophages and injury. Scarring correlated with a distinct set of 172 transcripts associated with B cells, plasma cells, and others of unknown significance. The strongest correlation was with four mast cell transcripts. In biopsies with scarring, high expression of mast cell transcripts was associated with reduced graft survival and poor functional recovery. In renal allograft biopsies, infiltrates in scarred areas have implications for poor outcomes. Scarring is associated with a distinct pattern of inflammatory molecules, including B cell/immunoglobulin but particularly mast cell-associated transcripts, which correlated with poor outcomes. [source] Altered inflammatory responses in preterm children with cerebral palsyANNALS OF NEUROLOGY, Issue 2 2010Chang-Yi Lin BS Objective Perinatal inflammatory responses contribute to periventricular leukomalacia (PVL) and cerebral palsy (CP) in preterm infants. Here, we examined whether preterm children with CP had altered inflammatory responses when school-aged. Methods Thirty-two preterm children with PVL-induced CP (mean [±standard deviation] age, 7.2 ± 3.6 years) and 32 control preterm children with normal neurodevelopment (6.2 ± 2.2 years) and matched for gestational age were recruited. We measured tumor necrosis factor (TNF)-, levels in the plasma and the supernatants of peripheral blood mononuclear cells (PBMCs) before and after lipopolysaccharide (LPS) stimulation, and proinflammatory gene expression in the PBMCs. Results TNF-, expression was significantly higher in the plasma (p < 0.001) and supernatants of LPS-stimulated PBMCs (p = 0.003) in the CP group than in the control group. After LPS stimulation, the intracellular TNF-, level in the PBMCs was significantly lower in the control group (p = 0.016) and significantly higher in the CP group (p = 0.01). The CP group also had, in their nonstimulated PBMCs, significantly higher mRNA levels of inflammatory molecules: toll-like receptor 4 (TLR-4) (p = 0.0023), TNF-, (p = 0.0016), transforming growth factor-,,activated kinase 1 (p = 0.038), I,B kinase-, (p = 0.029), and c-Jun N-terminal kinase (p = 0.045). The TLR-4 mRNA levels in the PBMCs were highly correlated with TNF-, levels in LPS-stimulated PBMCs (Spearman rank correlation = 0.38, p = 0.03). Interpretation The finding that preterm children with PVL-induced CP have altered inflammatory responses indicates the possibility of programming effect of PVL or inflammation-related events during early life. ANN NEUROL 2010;68:204,212 [source] Effect of interleukin-32, on differentiation of osteoclasts from CD14+ monocytesARTHRITIS & RHEUMATISM, Issue 2 2010Yong-Gil Kim Objective Interleukin-32 (IL-32) induces various inflammatory molecules in human monocytes and differentiation of monocytes into macrophage-like cells. This study was undertaken to evaluate the effects of IL-32,, the most biologically active isoform, on the differentiation and activation of osteoclasts. Methods CD14+ monocytes were obtained from healthy volunteers, and samples of synovial tissue and synovial fluid were obtained from patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). The concentration and expression levels of IL-32, in RA and OA samples were evaluated by enzyme-linked immunosorbent assay and immunoblotting, respectively. To examine the osteoclastogenic effects and functional activities, isolated monocytes were treated with either IL-32, or IL-17 in the presence or absence of soluble RANKL (sRANKL) on a culture system and on Osteologic disks. The expression of RANKL and osteoprotegerin (OPG) messenger RNA (mRNA) in RA fibroblast-like synoviocytes (FLS) was measured using reverse transcription,polymerase chain reaction (PCR) and real-time PCR. Results The concentration and expression levels of IL-32, were higher in the RA samples than in the OA samples. Upon costimulation with sRANKL, the osteoclast count and resorbed area increased more significantly in the IL-32,,stimulated cultures than in those stimulated with IL-17. In the IL-32,,treated group without sRANKL stimulation, osteoclasts were differentiated, but the cells displayed low resorption activity. In RA FLS, RANKL mRNA expression increased in the presence of both IL-32, and IL-17. However, transcription of OPG decreased following IL-32, stimulation, resulting in a significant increase in the RANKL:OPG ratio. Conclusion Our results suggest that IL-32, is a potent mediator of active osteoclast generation in the presence of sRANKL. Moreover, this novel cytokine creates more favorable conditions for osteoclastogenesis in the RA joint by increasing the RANKL:OPG ratio in FLS. [source] Novel markers of inflammation identified in tumor necrosis factor receptor,associated periodic syndrome (TRAPS) by transcriptomic analysis of effects of TRAPS-associated tumor necrosis factor receptor type I mutations in an endothelial cell lineARTHRITIS & RHEUMATISM, Issue 1 2009Susana L. Rebelo Objective To analyze the effects of tumor necrosis factor receptor,associated periodic syndrome (TRAPS),associated mutant tumor necrosis factor receptor type I (TNFRI) expression in a cell type directly relevant to the inflammation in TRAPS, and to identify novel markers associated with mutant TNFRI expression. Methods Transcriptome analysis on 30,000 human genes was performed on SK-Hep-1 human endothelial cells transfected with either wild-type (WT) or TRAPS-associated mutant TNFRI. Quantitative reverse transcriptase,polymerase chain reaction and protein expression levels measured by enzyme-linked immunosorbent assay verified transcriptional changes for selected genes both in supernatants from cells expressing mutant TNFRI and in patient plasma. Results Cells expressing mutant TNFRI showed up-regulation of multiple proinflammatory genes relative to WT transfectants, including genes for pentraxin 3, granulocyte,macrophage colony-stimulating factor, granulocyte colony-stimulating factor, CCL2, and CCL5, which were also expressed as proteins. In addition, the expression of most of these markers was increased in the plasma and peripheral blood mononuclear cells from TRAPS patients relative to those from healthy controls. The cysteine mutations (C33Y and C52F), which are associated with a more severe clinical phenotype, induced more genes than the low-penetrance mutation R92Q, which is associated with a milder phenotype. The expression of most genes was induced by a death domain (DD),dependent mechanism, since they were not induced by expression of TNFRI mutants with an inactivated DD. Conclusion TRAPS-associated TNFRI mutants induce the expression of multiple genes encoding inflammatory molecules, cellular receptors, transcription factors, and regulators of apoptosis in endothelial cells that require the cytoplasmic signaling properties of the receptor. Different mutants have specific expression profiles, indicating mutation-specific effects. The expression of some of these markers was also elevated in samples from TRAPS patients. [source] Review article: Is obesity an inflammatory illness?BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2006Role of low-grade inflammation, macrophage infiltration in human white adipose tissue There are at least two scientific evidences of human obesity as a chronic inflammatory illness: first, the well-described moderate increase of inflammatory factors in the circulation in obese subjects, and second, the recent identification of macrophage cells infiltrating the white adipose tissue (WAT). These observations led to a revision of the physiopathology of obesity and its co-morbidities. It has been suggested that the ,low-grade' inflammatory state associates with metabolic and cardiovascular complications of obesity. Weight loss is able to improve this inflammatory state by both significantly decreasing circulating inflammatory molecules and macrophage cell infiltration in WAT depots. However, the mechanisms of WAT macrophage recruitment into the adipose tissue and their role in obesity complications have not been defined. This review aims to point out the knowledge on inflammatory cytokines associated with obesity and focuses on macrophage infiltration in human WAT, discussing their recruitment and role. The interactions of macrophages with adipocytes will certainly be the subject of intense investigations in the future. [source] Respiratory syncytial virus and neutrophil activationCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005E. L. Bataki Summary Respiratory syncytial virus infects almost all children by 2 years of age. Neutrophils are the predominant airway leucocytes in RSV bronchiolitis and they are activated in the presence of infection. However it is not clear whether RSV can directly signal to activate neutrophil cytotoxic function. To investigate this we have used a preparation of RSV washed using a new centrifugal diafiltration method to rapidly remove inflammatory molecules produced by the epithelial cells used to propagate the RSV stock. Human neutrophils were isolated from peripheral blood and activated with either the unwashed crude RSV preparations or the purified intact RSV. Neutrophils were also challenged with purified RSV G-glycoprotein. The effect of challenging human neutrophils with these preparations of intact RSV, or the RSV G-glycoprotein, was assessed by measuring the cell surface expression of CD11b and CD18b, the phagocytic oxidative burst, and intracellular release of calcium pools. Neutrophils challenged with the washed RSV exhibited significantly lower activation of surface marker expression (P < 0·001) and oxidative burst (P < 0·001) than those challenged with unwashed virus or with virus free supernatant. There was no increase in intracellular calcium release on exposure to the washed RSV. Purified G glycoprotein did not stimulate neutrophils, whilst the use of a blocking antibody to the F protein did not prevent unwashed RSV from activating cytotoxic responses. These results suggest that neutrophils have no innate signalling system that recognizes RSV but they are activated at sites of RSV infection as a result of the cytokines and inflammatory molecules released by virally infected cells. [source] The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studiesCLINICAL ENDOCRINOLOGY, Issue 5 2010Marina Muzza Summary Objective, The recent concept that oncogenes responsible for thyroid neoplastic transformation are able to elicit an inflammatory protumourigenic microenvironment raises interest in further studies on papillary thyroid cancer (PTC) associated with thyroid autoimmunity. Patients, The clinical and molecular features, and the expression of inflammation-related genes, were investigated in a large series of PTCs with and without associated thyroiditis (groups A, n = 128 and B, n = 215). Results, The two groups did not show significant differences in clinical and prognostic features, whereas they harboured a significantly different genetic background (P = 0·001), with RET/PTC1 being more represented in PTCs associated with autoimmunity, and BRAFV600E in patients with PTC alone. A RET/PTC rearrangement was also found in 41% of non-neoplastic thyroiditis tissues, contralateral to tumours harbouring either RET/PTC or BRAF mutations. The expression of genes encoding CCL20, CXCL8 and l -selectin was significantly higher in PTC specimens (either with RET/PTC, BRAFV600E or unknown genetic lesion) compared with normal thyroid samples. On the contrary, thyroiditis showed l -selectin expression levels even higher than PTCs, but CCL20 and CXCL8 levels comparable with normal tissues. Conclusions, The present data extend the knowledge about the tight relationships among oncogenes, thyroiditis and thyroid cancer. A different genetic background among PTCs with and without associated autoimmunity has been firstly demonstrated. The strong association between RET/PTC1 and thyroiditis points to a critical role of this oncoprotein in the modulation of the autoimmune response. Moreover, preliminary expression studies, indicating enhanced expression of inflammatory molecules in PTCs, suggest a proinflammatory, nonautoimmune relationship between thyroiditis and thyroid cancer. [source] | ||||||||||||||||||||||