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

There are many humoral factors that regulate the migration of mast cell progenitors from the blood into tissues and the migration of mature mast cells within tissues, leading to the rapid accumulation that occurs in diverse pathological conditions. First of all, mast cell migration is stimulated by some chemokines, such as RANTES, eotaxin, and IL-8. Moreover, many cytokines induce the migration of mast cells (i.e. SCF, TNF, IL-15). Finally, the migration of mast cells is also stimulated by many other humoral factors, including those involved in inflammatory process, such as C3a, C5a, histamine, PAF, and CRP. Because mast cells play an essential role in diverse physiological and pathological processes, it seems to be of great importance to know the mechanisms underlying the migration of immature and mature mast cells. However, current knowledge about these processes is still insufficient.
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PMID:[The regulation of mast cell migration. Part 2: mast cell chemoattractants]. 1790 17

Over production of interleukin (IL)-15 and IL-17 was observed in synovial fluids of rheumatoid arthritis (RA) patients. IL-15 activates T cells and induces IL-17 production whereas IL-17 stimulates synoviocytes to release several mediators of inflammation including IL-6, TNF-alpha, IL-8, and CCL2. Thus, it is presumed that IL-15 and IL-17 play important roles in the pathogenesis of RA. Based on these results, we investigated a new anti-rheumatic drug targets IL-15 and IL-17 and found a new pyrazoleanilide derivative, Y-320 that inhibits IL-15-induced IL-17 production by T cells at 10-nM order. Therapeutic treatment with Y-320 (0.3 to 3 mg/kg orally) significantly inhibited the progression of arthritis and joint destruction in type II collagen-induced arthritis (CIA) in DBA/1J mice. Y-320 inhibited the elevation of IL-17 mRNA expression in the joint of CIA mice. Concomitant treatment with Y-320 and anti-mouse TNF-alpha antibody showed a synergistic effect in mouse CIA. Moreover, therapeutic treatment with Y-320 (0.3 and 1 mg/kg orally) ameliorated CIA in cynomolgus monkeys. Our results suggest that Y-320, a small molecule inhibitor for IL-17 production, is a candidate for the new class of orally active anti-rheumatic drug.
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PMID:[A new orally active anti-rheumatic drug targets IL-15 and IL-17]. 1798 77

The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-gamma-producing CD8(+) and CD4(+) effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-gamma was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication.
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PMID:Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid. 1800 37

Skeletal muscle fibers express several cytokines, including interleukin (IL)-6, IL-8, and IL-15. Solid evidence exists that muscular IL-6 and IL-8 are regulated by muscle contractions, at both the mRNA and the protein levels. IL-6 increases insulin-stimulated glucose disposal and fatty acid oxidation in humans in vivo. Both IL-6 and IL-8 are released from working skeletal muscle, but because IL-6 contributes to the systemic circulation only a small transient net release of IL-8 is found from working muscle, suggesting that IL-8 may exert its effects locally in the muscle. IL-15 is a recently discovered growth factor, which is highly expressed in skeletal muscle. Interestingly, although IL-15 has been demonstrated as having anabolic effects on skeletal muscle in vitro and in vivo, it seems to play a role in reducing adipose tissue mass, and a role for IL-15 in muscle-fat cross-talk has been hypothesized. In conclusion, muscle-derived cytokines appear to have important roles in metabolism, and exercise plays a role in orchestrating the interplay between cytokines and metabolism.
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PMID:The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15. 1805 6

To study the immune responses of porcine intestinal epithelial cells to gram-negative bacteria via toll-like receptors (TLRs), originally established porcine intestinal epitheliocyte (PIE) cells were treated with lipopolysaccharide (LPS) or swine-specific enterotoxigenic Escherichia coli (ETEC). Real-time quantitative PCR revealed that PIE cells expressed TLR1-9 and MD-2 mRNAs, preferentially expressed TLR4/MD-2. Immunostaining of PIE cells revealed that TLR4 was precisely expressed in PIE cells at the protein level. PIE cells treated with LPS had up-regulated expression of several TLRs (TLR2, 3, 4, 5 and 8), type 1 helper T (Th1) cytokines (interleukin (IL)-1alpha, IL-1beta, IL-6, IL-15, 18, leukemia inhibitory factor (LIF), and interferon (IFN)-beta), and chemokines (monocyte chemoattractant protein (MCP)-1 and IL-8). ETEC enhanced the expression of TLR2, Th1 type cytokines (IL-1alpha, IL-12p35 and IL-6) and chemokines (MCP-1 and IL-8). These results indicate that PIE induces inflammatory responses by up-regulating Th1 cytokines and chemokines in response to LPS or ETEC, suggesting that PIE is a useful cell line for studying inflammatory responses via TLR4/MD-2 in intestinal epithelial cells.
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PMID:Toll-like receptor 4 and cytokine expression involved in functional immune response in an originally established porcine intestinal epitheliocyte cell line. 1808 46

Exposing blood to an artificial surface results in a systemic inflammatory response, including cytokine release and complement activation. We studied the artificial surface-induced inflammation in human whole blood using an extensive panel of inflammatory mediators including proinflammatory cytokines, chemokines and growth-factors and investigated the role of the complement system in the induction of this response. Using multiplex technology, 27 different inflammatory mediators were measured after circulating blood for 4 hours in polyvinyl chloride tubing. The C3 inhibitor compstatin was used to block complement activation. A significant (p < 0.05) increase in 14 of the 27 mediators was induced by the surface, of which 7 were chemokines (IL-8, MCP-1, MIP-1alpha, MIP-1beta, RANTES, eotaxin and IP-10) and 5 were growth-factors (G-CSF, GM-CSF, VEGF, PDGF and FGF). The traditional proinflammatory cytokines like IL-1beta, TNFalpha and IL-6 were not induced, although IL-6, as well as IL-15 and IL-17 increased if the surface was coated with highly bioincompatible laminaran. Inhibition of complement activation with compstatin significantly (p < 0.05) reduced the formation of 12 of the 14 mediators. For 10 of the 12 mediators, the inhibition was by 2/3 or more, for the remaining two the inhibition was more moderate. A highly biocompatible heparin-coated PVC surface was used as negative control and completely abolished the whole inflammatory response. The artificial surface PVC markedly induced a broad spectrum of chemokines and growth-factors, which was largely dependent on activation of complement.
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PMID:The artificial surface-induced whole blood inflammatory reaction revealed by increases in a series of chemokines and growth factors is largely complement dependent. 1808 44

Interleukin-15 is a cytokine produced by a wide range of different cell types, including macrophages, in response to lipopolysaccharide or microbial infection. This cytokine may play a crucial role in the activation of phagocytic cells against pathogens, especially during innate immune response. The effects of IL-15 on human polymorphonuclear leukocyte fungicidal activity against a highly virulent Paracoccidioides brasiliensis strain were investigated. Pretreatment of human neutrophils from healthy individuals with IL-15 for 18 hours increased cell fungicidal activity in a dose-dependent manner. In addition, the exposure to IL-15 induced an increase in neutrophil oxidative burst as evaluated by superoxide anion and H(2)O(2) release. Catalase inhibited fungicidal activity supporting a role for H(2)O(2) in fungus killing. In contrast, IL-8 and TNF-alpha levels were not affected by IL-15 suggesting that its effects were not mediated by these cytokines. Together, these results show that IL-15 is a potent stimulant of antifungal activities in human neutrophils, at least in part by a mechanism dependent on oxidative metabolism.
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PMID:Interleukin-15 increases Paracoccidioides brasiliensis killing by human neutrophils. 1808 32

Interleukin (IL)-17 is a 30- to 35-kDa homodimeric polypeptide cytokine cloned in 1993 and originally named cytotoxic T lymphocyte-associated antigen-8 (CTLA-8). Sequencing the human genome resulted in the discovery of an additional five members of the IL-17 family that were consecutively named IL-17B to IL-17F. IL-17A is exclusively produced by a newly identified CD4+ T-helper subset that was recently named Th17. Differentiation of these cells from naive CD4+ T cells requires both TGF-beta and IL-6. IL-15 and, especially, IL-23 are required for these cells' survival and efficient IL-17 production. IL-17 binding to an IL-17 receptor expressed on epithelial, endothelial, and fibroblastic stromal cells triggers the activation of transcription factor NF-kappaB and mitogen-activated protein kinase (p-38), which in turn results in the secretion of IL-1, TNF-alpha, IL-6, IL-8, or prostaglandin E2. The IL-17 family plays a key role in the regulation of immune and inflammatory response, in the homeostasis of several tissues, and the progression of autoimmune diseases. In addition, IL-17 exerts synergistic effects with TNF-alpha and IL-1 in the induction of joint inflammation and cartilage and joint destruction. Given these properties, it is not surprising that in certain pathological conditions, for example rheumatoid arthritis, Th17 cells emerge as a new pathological cell type that, by IL-17 production and release, contributes to their pathogeneses.
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PMID:The function of interleukin 17 in the pathogenesis of rheumatoid arthritis. 1821 63

The impressive correlation between cardiovascular disease and alterations in glucose metabolism has raised the likelihood that atherosclerosis and type 2 diabetes may share common antecedents. Inflammation is emerging as a conceivable etiologic mechanism for both. Interleukins are regulatory proteins with ability to accelerate or inhibit inflammatory processes, and matrixins are prepro enzymes responsible for the timely breakdown of extracellular matrix. Interleukins (ILs) are classified based on their role in diabetes and atherosclerosis, hypothesizing that each interleukin acts on both diseases in the same direction - regardless if harmful, favorable or neutral. They are clustered into three groups: noxious (the 'bad', 8 members), comprising IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-17 and IL-18; protective (the 'good', 5 members), comprising IL-4, IL-10, IL-11, IL-12 and IL-13; and 'aloof' , comprising IL-5, IL-9, IL-14, IL-16 and IL-19 through IL-29 (15 members). Each group presented converging effects on both diseases. IL-3 was reluctant to clustering and IL-30 through 33 were not included due to the scarce available data. It may be seen that (1) favorable effects of a given interleukin on either diabetes or atherosclerosis predicts similar effects on the other; (2) equally, harmful interleukin effects on one disease can be extrapolated to the other, and (3) absence of influence of a given interleukin on one of these diseases forecasts lack of effects on the other. Matrixins seem to present a similar pathophysiological pattern. These facts further support the unifying etiologic theory of diabetes and heart disease, emphasizing the importance of a cardiovascular diabetologic approach to these cytokines for future research. A pharmacologic simultaneous targeting of interleukins and matrixins might provide an effective means to concurrently control both atherosclerosis and diabetes.
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PMID:Biomarkers in cardiovascular diabetology: interleukins and matrixins. 1823 Sep 55

To investigate the influence of genetic differences in the MHC on susceptibility to avian coccidiosis, M5.1 and M15.2 B-haplotype-disparate Fayoumi chickens were orally infected with live Eimeria maxima oocysts, and BW gain, fecal oocyst production, and expression of 14 immune-related genes were determined as parameters of protective immunity. Weight loss was reduced and fecal parasite numbers were lower in birds of the M5.1 line compared with M15.2 line birds. Intestinal intraepithelial lymphocytes from M5.1 chickens expressed greater levels of transcripts encoding interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), IL-6, IL-8, IL-12, IL-15, IL-17A, inducible nitric oxide synthase, and lipopolysaccharide-induced tumor necrosis factor-alpha factor and lower levels of mRNA for IFN-alpha, IL-10, IL-17D, NK-lysin, and tumor necrosis factor superfamily 15 compared with the M15.2 line. In the spleen, E. maxima infection was associated with greater expression levels of IFN-gamma, IL-15, and IL-8 and lower levels of IL-6, IL-17D, and IL-12 in M5.1 vs. M15.2 birds. These results suggest that genetic determinants within the chicken MHC influence resistance to E. maxima infection by controlling the local and systemic expression of immune-related cytokine and chemokine genes.
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PMID:Immune-related gene expression in two B-complex disparate genetically inbred Fayoumi chicken lines following Eimeria maxima infection. 1828 68


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