Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Little is known about the regulation and coordinated expression of genes involved in the innate host response to Candida albicans. We therefore examined the kinetic profile of gene expression of innate host defense molecules in normal human monocytes infected with C. albicans using microarray technology. Freshly isolated peripheral blood monocytes from five healthy donors were incubated with C. albicans for 0 to 18 h in parallel with time-matched uninfected control cells. RNA from monocytes was extracted and amplified for microarray analysis, using a 42,421-gene cDNA chip. Expression of genes encoding proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 (IL-1), IL-6, and leukemia inhibitory factor, was markedly enhanced during the first 6 h and coincided with an increase in phagocytosis. Expression of these genes returned to near baseline by 18 h. Genes encoding chemokines, including IL-8; macrophage inflammatory proteins 1, 3, and 4; and monocyte chemoattractant protein 1, also were strongly up-regulated, with peak expression at 4 to 6 h, as were genes encoding chemokine receptors CCR1, CCR5, CCR7, and CXCR5. Expression of genes whose products may protect monocyte viability, such as BCL2-related protein, metallothioneins, CD71, and SOCS3, was up-regulated at 4 to 6 h and remained elevated throughout the 18-h time course. On the other hand, expression of genes encoding T-cell-regulatory molecules (e.g., IL-12, gamma interferon, and transforming growth factor beta) was not significantly affected during the 18-h incubation. Moreover, genes encoding IL-15, the IL-13 receptor (IL-13Ra1), and CD14 were suppressed during the 18-h exposure to C. albicans. Thus, C. albicans is a potent inducer of a dynamic cascade of expression of genes whose products are related to the recruitment, activation, and protection of neutrophils and monocytes.
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PMID:Expression of genes encoding innate host defense molecules in normal human monocytes in response to Candida albicans. 1590 1

Mesenchymal stem cells (MSCs), which are adherent stromal cells of a nonhematopoietic origin, have the ability to give rise to various differentiated cell types. MSCs regulate localization, self-renewal and differentiation of hematopoietic stem cells (HSCs) due to MSCs' secretion of cytokines and growth factors, the cell-to-cell interactions and the influence of the extracellular matrix proteins. Using RT-PCR analysis, we examined the expression levels of cytokines and growth factors from MSCs and their differentiated cell types, including osteoblasts, adipocytes and endothelial cells. Cytokine and growth factor genes, including IL-6, IL-8, IL-11, IL-12, IL-14, IL-15, LIF, G-CSF, GM-CSF, M-SCF, FL and SCF, were found to be expressed in the MSCs. In contrast, there was no IL-1alpha, IL-1beta, or IL-7 expression observed. The IL-12, IL-14, G-CSF, and GM-CSF mRNA expression levels either disappeared or decreased after the MSCs differentiated into osteoblasts, adipocytes, and endothelial cells. Among the differentiated cells derived from MSCs, osteoblasts, adipocytes, and endothelial cells expressed the osteopontin, aP2, and the VEGFR-2 gene, respectively. These profiles could help determine future clinical applications of MSCs and their derivatives for cell therapy.
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PMID:Gene expression profile of cytokine and growth factor during differentiation of bone marrow-derived mesenchymal stem cell. 1591 13

Recently, mouse models for latent (LTB) and slowly progressive primary tuberculosis (SPTB) have been established. However, cytokine profiles during the two models are not well established. Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) we studied the expression levels of interleukin (IL)-2, IL-4, IL-10, IL-12, IL-15, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha during the course of LTB and SPTB in the lungs and spleens of B6D2F1Bom mice infected with the H37Rv strain of Mycobacterium tuberculosis (Mtb). The results show that, except for IL-4, cytokine expression levels were significantly higher during SPTB than LTB in both the lungs and spleens. During LTB, all the cytokines (except IL-2 in the lungs) had higher expression levels during the initial period of infection both in the lungs and spleens. During SPTB, the expression levels of IL-15 increased significantly from phases 1 to 3 in the lungs. The expression levels of IL-10, IL-12 and IFN-gamma increased significantly from 2 to 3 in the lungs. IL-10 and IL-15 increased significantly from phases 2 to 3, whereas that of TNF-alpha decreased significantly and progressively from phases 1 to 3 in the spleens. Over-expression of proinflammatory cytokines during active disease has been well documented, but factor(s) underlying such over-expression is not known. In the present study, there was a progressive and significant increase in the expression levels of IL-15, together with Th1 cytokines (IL-12 and IFN-gamma) during SPTB but a significant decrease during LTB. IL-15 is known to up-regulate the production of proinflammatory cytokines, IL-1beta, IL-8, IL-12, IL-17, IFN-gamma and TNF-alpha and has an inhibitory effect on activation-induced cell death. IL-15 is known to be involved in many proinflammatory disease states such as rheumatoid arthritis, sarcoidosis, inflammatory bowel diseases, autoimmune diabetes, etc. Our results, together with the above observations, suggest that IL-15 may play an important role in mediating active disease during Mtb infection.
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PMID:Cytokine profile during latent and slowly progressive primary tuberculosis: a possible role for interleukin-15 in mediating clinical disease. 1636 49

We herein discuss the impact of biological agents based on the ability of monoclonal antibodies to target specific molecules. This approach has given to clinical immunologists a spectrum of drugs able to manipulate the immune system. In the first session, we discuss drugs targeting T-cell function by: (1) targeting CD28 mediated costimulation (Abatacept and Belatacept); (2) interfering with interleukin-2 receptor (Basiliximab and Daclizumab); (3) blocking cell adhesion and homing (Alefacept, Efalizumab, Natalizumab). The second session is dedicated to drugs targeting cytokines or their receptors. The best known and largely experimented case is represented by drugs targeting tumor necrosis factor (TNF) (Infliximab, Adalilumab, Certolizumab) or its p75 receptor (Etanercept). However, newer products are now available to target other inflammatory cytokines including IL-6, IL-8, IL-12, IL-15, IL-18, IL-23. These agents have the potential to become powerful tools in the control of several immune-mediated diseases, especially auto-immune and inflammatory ones. They traslate into reality the prediction that antibodies will eventually become "magic bullets which seek their own target" (P. Ehrich, 1906).
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PMID:The impact of biological agents interfering with receptor/ligand binding in the immune system. 1647 34

There is much evidence that rheumatoid arthritis is closely linked to angiogenesis. Important angiogenic mediators have been demonstrated in synovium and tenosynovium of rheumatoid joints. VEGF (Vascular Endothelial Growth Factor), expressed in response to soluble mediators such as cytokines and growth factors and its receptors are the best characterized system in the angiogenesis regulation of rheumatoid joints. Moreover, other angiogenic mediators such as platelet-derived growth factor (PDGF), fibroblast growth factor-2 (FGF-2), epidermal growth factor (EGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), transforming growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, IL-8, IL-13, IL-15, IL-18, angiogenin, platelet activating factor (PAF), angiopoietin, soluble adhesion molecules, endothelial mediator (endoglin) play an important role in angiogenesis in rheumatoid arthritis. On the other hand, endostatin, thrombospondin-1 and -2 are angiogenic inhibitors in rheumatoid arthritis. The persistence of inflammation in rheumatoid joints is a consequence of an imbalance between these inducers and inhibitors of angiogenesis.
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PMID:Angiogenesis in rheumatoid arthritis. 1649 85

Cytokine mRNA expression in biopsies of Mycobacterium ulcerans-infected human tissue was investigated using real-time PCR, and the findings were correlated with the clinical stages of disease and histopathologies. A broad range of cytokine mRNAs were detected in 16 early nodules and 28 late-stage ulcers, including those for the Th1 cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) and the Th2 cytokine interleukin 10 (IL-10). IFN-gamma was strongly expressed in both nodules and ulcers, suggesting that a Th1 response begins early in the disease. There was a significantly higher expression of IL-8 and other proinflammatory cytokines in results from 32 biopsies with neutrophilia than in those from 12 biopsies without acute inflammation. Ten tissue samples containing granulomas showed high mRNA expression for IFN-gamma, IL-1beta, IL-12p35, IL-12p40, IL-15, and TNF-alpha relative to 34 tissue samples without granulomas. These results suggest that the human immune response to M. ulcerans is similar to that seen with some other mycobacteria despite the presence of the toxin mycolactone in the tissues.
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PMID:Cytokine mRNA expression in Mycobacterium ulcerans-infected human skin and correlation with local inflammatory response. 1662 30

Inflammatory processes are known to be involved at least in the early phase of complex regional pain syndrome type 1 (CRPS1). Blister fluid obtained from the involved extremities displayed increased amounts of proinflammatory cytokines IL-6 and TNFalpha compared with the noninvolved extremities. The aim of this paper is to investigate the involvement of mediators by measurement of several other cytokines using new detection techniques that enable multiple cytokine measurement in small samples. The use of a multiplex-25 bead array cytokine assay and Luminex technology enabled simultaneous measurement of representative (1) proinflammatory cytokines such as GM-CSF, IL-1beta, IL-1RA, IL-6, IL-8, and TNF-alpha; (2) Th1/Th2 distinguishing cytokines IFN-gamma, IL-2, IL-2R, IL-4, IL-5, and IL-10; (3) nonspecific acting cytokines IFN-alpha, IL-7, IL-12p40/p70, IL-13, IL-15, and IL-17; and (4) chemokines eotaxin, IP-10, MCP-1, MIP-1alpha, MIP-1beta, MIG, and RANTES. Although minimal detection levels are significantly higher in the bead array system than those in common ELISA assays, in blister fluid, IL-1RA, IL-6, IL-8, TNF-alpha, IL-12p40/p70, MCP-1, and MIP-1beta were detectable and increased in CRPS1 affected extremities. Levels of IL-6 and TNF-alpha simultaneously measured by ELISA (Sanquin Compact kit) and by multiplex-25 bead array assay (Biosource) were highly correlated (r = 0.85, P < .001 for IL-6 and r = 0.88, P < .001 for TNF-alpha). Furthermore, IP-10 and eotaxin were detectable but diminished in CRPS1, whereas detectable amounts of IL-10 were similar in involved and noninvolved extremities. Multiplex bead array assays are useful systems to establish the involvement of cytokines in inflammatory processes by measurements in blister fluids of CRPS1. Ten representative cytokines were detectable. However, detection levels and amounts measured are at least 3 times higher in the multiplex-25 array assay than in the ELISA assays used simultaneously for the measurement of cytokines.
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PMID:Multiplex bead array assay for detection of 25 soluble cytokines in blister fluid of patients with complex regional pain syndrome type 1. 1686

Dermatophytes cause intractable superficial infections in humans. Arthroderma benhamiae, a zoophilic dermatophyte, triggers severe inflammatory responses in humans, while Trichophyton tonsurans, an anthropophilic dermatophyte, triggers minimal ones. Cytokines and other factors derived from keratinocytes play important roles in inflammatory and immune responses in the skin. The authors performed an in vitro investigation to determine the human keratinocyte cytokine profiles during dermatophyte infection. The human keratinocyte cell line PHK16-0b was infected with A. benhamiae or T. tonsurans for 24 h, and the cytokines secreted were analysed using a human cytokine antibody array. Marked differences were observed in the cytokine profiles of the cells infected with the two dermatophytes. A. benhamiae infection resulted in the secretion of a broad spectrum of cytokines, including proinflammatory cytokines, chemokines, and immunomodulatory cytokines. In contrast, T. tonsurans-infected keratinocytes secreted only limited cytokines, including eotaxin-2, interleukin (IL)-8 and IL-16. cDNA microarray analysis confirmed that A. benhamiae infection upregulated genes encoding IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-13, IL-15, IL-16, IL-17 and interferon (IFN)-gamma, while T. tonsurans infection upregulated only a few genes, such as those encoding IL-1beta and IL-16. RT-PCR demonstrated that infection by both dermatophytes enhanced IL-8 mRNA expression in keratinocytes. These results suggest that A. benhamiae-induced secretion of several cytokines from keratinocytes may be involved in a severe inflammatory response, and that the limited cytokine secretion from keratinocytes in response to T. tonsurans infection may result in a minimal inflammatory response in the skin. These cytokine profiles may aid in proving the clinical features of dermatophytosis.
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PMID:Cytokine secretion profiles of human keratinocytes during Trichophyton tonsurans and Arthroderma benhamiae infections. 1691 46

Investigating the interaction of human endometrium and trophoblast during implantation is difficult in vitro and impossible in vivo. This study was designed to analyze the effect of trophoblast on endometrial stromal cells during implantation by comprehensive gene profiling. An in vitro coculture system of endometrial stromal cells with first-trimester trophoblast explants was established. Trophoblast and endometrial stromal cells were separated after 24 h. Gene expression of endometrial stromal cells after coculture was compared with the gene expression of endometrial stromal cells cultured alone by microarray analysis. We confirmed the expression of distinct genes using real-time PCR. Genes up-regulated included those for inflammatory response, immune response, and chemotaxis (pentraxin-related gene 3, chemokine ligands, IL-8, IL-1 receptors, IL-18 receptor, IL-15, IL-15 receptor, TNF-alpha-induced protein 6, and IL-6 signal transducer), regulators of cell growth (IGF-binding proteins 1 and 2) and signal transduction. Also up-regulated were genes for growth and development, glucose metabolism, and lipid metabolism: DKK-1, WISP, IGF-II, hydroxysteroid 11beta-dehydrogenase 1, hydroxyprostaglandin dehydrogenase 15, prostaglandin E synthase, prostaglandin F receptor, aldehyde dehydrogenase 1 family, member A3 and phosphatidic acid phosphatase type 2B. Other genes included genes for cell-cell signaling (pre-B-cell colony-enhancing factor 1), proteolysis, calcium ion binding, regulation of transcription, and others. Down-regulated genes included genes for proteolysis (MMP-11 and mitochondrial intermediate peptidase), genes for cell death (caspase 6, death-associated protein kinase 1, and histone deacetylase 5), transcription factors (sex determining region Y-box 4, dachshund homolog 1, ets variant gene 1, and zinc finger protein 84 and 435), and genes for humoral immune response (CD24 antigen). Trophoblast has a significant impact on endometrial stromal cell gene expression. Some of the genes regulated by trophoblast in endometrial stromal cells are already known to be regulated by progesterone and show the endocrine function of trophoblast during pregnancy. Others are genes so far unknown to play a role in endometrial-trophoblast interaction and open a wide field of investigation.
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PMID:Gene expression profiling of human endometrial-trophoblast interaction in a coculture model. 1694 11

There is a pressing need for adjuvants that will enhance the effectiveness of genetic vaccines. This is particularly important in cancer and infectious disease such as HIV and malaria for which successful vaccines are desperately needed. Here, we describe an approach to enhance immunogenicity that involves the activation of NF-kappaB by the transgenic expression of an intracellular signaling molecule, NF-kappaB-inducing kinase (NIK). In vitro, NIK increases dendritic cell antigen presentation in allogeneic and antigen-specific T cell proliferation assays by potently activating NF-kappaB and consequently up-regulating the expression of cytokines (TNF-alpha, IL-6, IL-12, IL-15, and IL-18), chemokines [IL-8, RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein-1alpha, monocyte chemoattractant protein-1, and monocyte chemoattractant protein-3], MHC antigen-presenting molecules (class I and II), and costimulatory molecules (CD80 and CD86). In vivo, NIK enhances immune responses against a vector-encoded antigen and shifts them toward a T helper 1 immune response with increased IgG2a levels, T cell proliferation, IFN-gamma production, and cytotoxic T lymphocyte responses more potently than complete Freund's adjuvant, a very efficacious T helper 1-inducing adjuvant. These findings define NIK, and possibly other inducers of NF-kappaB activation, as a potent adjuvant strategy that offers great potential for genetic vaccine development.
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PMID:Activation of NF-kappaB by the intracellular expression of NF-kappaB-inducing kinase acts as a powerful vaccine adjuvant. 1697 87


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