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)

Lipopolysaccharide (LPS) has been shown to induce proliferation of human T-lymphocytes only in the presence of monocytes and CD34(+) hematopoietic cells (HCs) from peripheral blood. This finding provided evidence of an active role of CD34(+) HCs during inflammation and immunological events. To investigate mechanisms by which CD34(+) HCs become activated and exert their immune-modulatory function, we used the human CD34(+) acute myeloid leukemia cell line KG-1a and CD34(+) bone marrow cells (BMCs). We showed that culture supernatants of LPS-stimulated mononuclear cells (SUP(LPS)) as well as tumor necrosis factor alpha (TauNF-alpha), but not LPS alone, can activate nuclear factor-kappaB in KG-1a cells. By cDNA subtraction and multiplex polymerase chain reaction, we revealed differential expression of cellular inhibitor of apoptosis protein-1, inhibitor of kappaB (IkappaB)/IkappaBalpha (MAD-3), and intercellular adhesion molecule-1 (ICAM-1) in SUP(LPS)-stimulated KG-1a cells and up-regulation of interferon (IFN)-inducible T cell-chemoattractant, interleukin (IL)-8, macrophage-inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, RANTES, CD70, granulocyte macrophage-colony stimulating factor, and IL-1beta in stimulated KG-1a cells and CD34(+) BMCs. Although monokine induced by IFN-gamma, IFN-inducible protein 10, and IFN-gamma were exclusively up-regulated in KG-1a cells, differential expression of monocyte chemoattractant protein-1 (MCP-1), macrophage-derived chemokine, myeloid progenitor inhibitory factor-2, and IL-18 receptor was only detectable in CD34(+) BMCs. More importantly, CD34(+) BMCs stimulated by TNF-alpha also showed enhanced secretion of MCP-1, MIP-1alpha, MIP-1beta, and IL-8, and increased ICAM-1 protein expression could be detected in stimulated KG-1a cells and CD34(+) BMCs. Furthermore, we revealed that T cell proliferation can be induced by TNF-alpha-stimulated KG-1a cells, which is preventable by blocking anti-ICAM-1 monoclonal antibodies. Our results demonstrate that CD34(+) HCs have the potential to express a variety of immune-regulatory mediators upon stimulation by inflammatory cytokines including TNF-alpha, which may contribute to innate- and adaptive-immune processes.
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PMID:Induction of various immune modulatory molecules in CD34(+) hematopoietic cells. 1474 40

In cattle and other ruminants, infection with the intracellular pathogen Mycobacterium avium subsp. paratuberculosis results in a granulomatous enteritis (Johne's disease) that is often fatal. The key features of host immunity to M. avium subsp. paratuberculosis infection include an appropriate early proinflammatory and cytotoxic response (Th1-like) that eventually gives way to a predominant antibody-based response (Th2-like). Clinical disease symptoms often appear subsequent to waning of the Th1-like immune response. Understanding why this shift in the immune response occurs and the underlying molecular mechanisms involved is critical to future control measures and diagnosis. Previous studies have suggested that M. avium subsp. paratuberculosis may suppress gene expression in peripheral blood mononuclear cells (PBMCs) from infected cows, despite a continued inflammatory reaction at sites of infection. In the present study, we tested the hypothesis that exposure to M. avium subsp. paratuberculosis suppresses a proinflammatory gene expression pattern in PBMCs from infected cows. To do this, we examined expression of genes encoding interleukin-1alpha (IL-1alpha), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-16, and IL-18, as well as genes encoding gamma interferon (IFN-gamma), transforming growth factor beta (TGF-beta), and tumor necrosis factor alpha (TNF-alpha), in PBMCs, intestinal lesions, and mesenteric lymph nodes of cattle naturally infected with M. avium subsp. paratuberculosis. Cytokine gene expression in these cells and tissues was compared to expression in similar cells and tissues from control uninfected cattle. Our comprehensive results demonstrate that for most cytokine genes, including the genes encoding IFN-gamma, TGF-beta, TNF-alpha, IL-1alpha, IL-4, IL-6, IL-8, and IL-12p35, differential expression in PBMCs from infected and control cattle did not require stimulation with M. avium subsp. paratuberculosis. In fact, stimulation with M. avium subsp. paratuberculosis tended to reduce the differential expression observed in infected and uninfected cows for genes encoding IFN-gamma, IL-1alpha, and IL-6. Only IL-10 gene expression was consistently enhanced by M. avium subsp. paratuberculosis stimulation of PBMCs from subclinically infected cattle. In ileal tissues from M. avium subsp. paratuberculosis-infected cattle, expression of the genes encoding IFN-gamma, TGF-beta, IL-5, and IL-8 was greater than the expression in comparable tissues from control uninfected cattle, while expression of the gene encoding IL-16 was lower in tissues from infected cattle than in control tissues. Mesenteric lymph nodes draining sites of M. avium subsp. paratuberculosis infection expressed higher levels of IL-1alpha, IL-8, IL-2, and IL-10 mRNA than similar tissues from control uninfected cattle expressed. In contrast, the genes encoding TGF-beta and IL-16 were expressed at lower levels in lymph nodes from infected cattle than in tissues from uninfected cattle. Taken together, our results suggest that cells or other mechanisms capable of limiting proinflammatory responses to M. avium subsp. paratuberculosis develop in infected cattle and that a likely place for development and expansion of these cell populations is the mesenteric lymph nodes draining sites of infection.
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PMID:Cytokine gene expression in peripheral blood mononuclear cells and tissues of cattle infected with Mycobacterium avium subsp. paratuberculosis: evidence for an inherent proinflammatory gene expression pattern. 1497 46

Measurements of cervical immunity are important for evaluating immune responses to infections of the cervix and to vaccines for preventing those infections. Three ophthalmic sponges, Weck-Cel, Ultracell, and Merocel, were loaded in vitro with interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-15, IL-18, gamma interferon (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), immunoglobulin A (IgA), or IgG, and sponges were extracted and evaluated for total recovery by enzyme-linked immunosorbent assay (ELISA). There was excellent (>75%) recovery for all immune markers from all three devices except for IL-6, which was poorly recovered (<60%) for all sponge types, IFN-gamma, which was poorly recovered from both Weck-Cel and Ultracell sponges but was completely recovered from Merocel sponges, and IL-4, which was poorly recovered from Weck-Cel sponges but was completely recovered from Ultracell or Merocel sponges. We then compared the absolute recovery of selected markers (IL-10, IL-12, IgG, and IgA) from cervical secretion specimens collected from women using each type of sponge. There were no significant differences in the recoveries of IL-10, IL-12, and IgG from cervical specimens collected by any type of ophthalmic sponge, but there was reduced IgA recovery from Merocel sponges. However, the variability in these measurements attributable to sponge types (1 to 3%) was much less than was attributable to individuals (45 to 72%), suggesting that differences in sponge type contribute only in a minor way to these measurements. We infer from our data that the three collection devices are adequate for the measurements of IL-1 beta, IL-2, IL-5, IL-12, IL-15, IL-18, and IgG. Merocel may be a better ophthalmic sponge for the collection of cervical secretions and measurements of IL-4, IL-8, IL-10, GM-CSF, and IFN-gamma, but our data from clinical specimens, not in vitro-loaded sponges, suggested the possibility of reduced recovery of IgA. These findings require confirmation.
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PMID:Comparison of ophthalmic sponges for measurements of immune markers from cervical secretions. 1501 94

Cytokines interfere with steroidogenesis at the level of the adrenals, testes, and ovaries. Within the adrenal, macrophages, and lymphocytes, physiologically widely infiltrating the adrenal cortex, and adrenocortical, and chromaffin cells produce cytokines, as IL-1, IL-6, TNFalpha, leukemia inhibitory factor (LIF), and IL-18 which have a key role in the immune-adreno-cortical communication. In addition to cytokines interacting with adrenal function, cytokine independent mechanisms are responsible for a cell to cell-mediated immune regulation of the adrenal. The importance of this immune-endocrine cross-talk becomes evident in the case of autoimmune and inflammatory diseases being necessary for an adequate adrenal stress response. Secretory products of macrophages are involved in the regulation of steroidogenesis, Sertoli cell activity, and germ cell survival in the human testes. In rats, IL-1 is involved in the paracrine regulation of Leydig cell steroidogenesis. IL-6 has been suggested to exert adverse effects on the male reproductive function, inducing persistent testicular resistance to luteinizing hormone (LH) action and/or suppression of Leydig cell steroidogenesis. Cytokines such as IL-8 and MCP-1 (monocyte chemotactic protein-1) are involved in follicular development and atresia, ovulation, steroidogenesis, and corpus luteum function. In undifferentiated ovarian cells TNF and IL-1 inhibit steroidogenesis, whereas in differentiated ovaries these cytokines stimulate progesterone synthesis. Some ovarian cancer cells secrete TNF and IL-1 which stimulate growth of these cells. In conclusion, cytokines interact with steroidogenesis in a systemic and complex manner, influencing development, function, and hormone production of the adrenals, testes, and ovaries.
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PMID:Cytokines and steroidogenesis. 1502 86

Interleukin (IL)-18 is a novel cytokine expressing at inflammatory lesion. In this study, to evaluate the clinical significance of IL-18 determination, we have examined serum IL-18, inflammation markers, sFas, and sFas-ligand concentrations in patients with rheumatoid arthritis(RA). Serum was obtained from 56 RA patients aged 35-74 years, 16 osteoarthritis (OA) patients aged 36-78 years and 178 healthy subjects aged 20-72 years and IL-18 was measured by ELISA. Serum IL-18 concentrations in RA (240.1 +/- 15.6 pg/ml, mean +/- SE) were significantly higher than OA (151.8 +/- 12.7 pg/ml, p < 0.005) and healthy controls(141.5 +/- 26.1 pg/ml, p < 0.001). Serum IL-18 levels were significantly increased in II to IV stages of RA (stage II; 218.6 +/- 31.2 pg/ml, stage III; 258.7 +/- 38.4 pg/ml, stage IV; 231.6 +/- 13.1 pg/ml) than those in OA. Furthermore, a positive correlation was observed between serum IL-18 concentration and serum Fas level in patients with RA (r = 0.472), whereas there was no significant correlation between serum IL-18 and sFas-ligand or other inflammatory markers (CRP, RF, CA-RF, IL-6, and IL-8). The present study showed that serum IL-18 level increased in RA, but it is unknown how IL-18 is involved in the pathogenesis of RA. Further study will be necessary to clarify the role of IL-18 in RA.
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PMID:[Clinical significance of serum IL-18 determination in rheumatoid arthritis]. 1502 13

Proinflammatory cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-18 are key mediators of joint inflammation during rheumatoid arthritis (RA). This chronic inflammation may result from a non-specific innate immune response that could be triggered by a wide variety of microorganisms, because numerous bacterial fragments have been identified in the joints of RA patients. As we have demonstrated previously that protein I/II, a pathogen-associated molecular pattern (PAMP) from oral streptococci, triggers IL-6 and IL-8 gene expression and release from either THP-1 cells or fibroblast-like synoviocytes (FLSs), we next explored the capacity of protein I/II to induce the synthesis and release of IL-18 in THP-1 cells and in FLSs isolated from either RA or osteoarthritis (OA) patients. We demonstrate that protein I/II induced IL-18 mRNA in both THP-1 cells and FLSs but, in contrast to THP-1 cells, gene expression was not associated with the synthesis of the corresponding protein in FLSs. Furthermore, our studies revealed that FLSs did not express the biologically inactive precursor, pro-IL-18, in response to protein I/II. Using actinomycin D, we also showed that IL-18 mRNA is unstable in FLSs. Taken together, these data indicate that lack of IL-18 release from activated FLSs results from a defect in translation of IL-18 mRNA into pro-IL-18 because of rapid degradation of IL-18 mRNA.
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PMID:Impaired release of IL-18 from fibroblast-like synoviocytes activated with protein I/II, a pathogen-associated molecular pattern from oral streptococci, results from defective translation of IL-18 mRNA in pro-IL-18. 1510 99

To assess the physiologic interactions between the infective stage of Brugia malayi--one of the extracellular parasites responsible for lymphatic filariasis in humans--and the APC with which they come in contact during their development and routes of travel, we have investigated the interaction between the infective stage (L3) of B. malayi and human Langerhans cells (LC) in the skin. Our data indicate that live L3 result in increased migration of LC from the epidermis without affecting the viability of these cells and up-regulation of the IL-18 cytokine involved in LC migration. Live L3 also result in down-regulation of MHC class I and II on the LC cell surface. Additionally, microarray data indicate that live L3 significantly down-regulated expression of IL-8 as well as of multiple genes involved in Ag presentation, reducing the capacity of LC to induce CD4(+) T cells in allogeneic MLR, and thus resulting in a decreased ability of LC to promote CD4(+) T cell proliferation and production of IFN-gamma and IL-10. These data suggest that L3 exert a down-regulatory response in epidermal LC that leads to a diminished capacity of these cells to activate CD4(+) T cells.
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PMID:Filaria-induced immune evasion: suppression by the infective stage of Brugia malayi at the earliest host-parasite interface. 1512 11

IL-1 and IL-18 are members of the IL-1 family of ligands, and their receptors are members of the IL-1 receptor family. Although several biological properties overlap for these cytokines, differences exist. IL-18 uniquely induces IFN-gamma from T lymphocytes and natural killer cells but does not cause fever, whereas fever is a prominent characteristic of IL-1 in humans and animals. In the present study, human epithelial cells were stably transfected with the IL-18 receptor beta chain and responded to IL-18 with increased production of IL-1alpha, IL-6, and IL-8. Five minutes after exposure to either cytokine, phosphorylation of mitogen activated protein kinase (MAPK) p38 was present; specific inhibition of p38 MAPK reduced IL-18 activity to background levels. Whereas IL-1beta induced the expression of the NF-kappaB-reporter gene and was suppressed by competitive inhibition of NF-kappaB binding, IL-18 responses were weak or absent. In contrast to IL-1beta, IL-18 also did not activate degradation of the NF-kappaB inhibitor. After 4 h, both cytokines induced comparable levels of mRNA for the chemokine IL-8 but, in the same cells, steady-state levels of cyclooxygenase (COX)-2 mRNA were high after IL-1beta but low or absent after IL-18. After 30 h, IL-18-induced COX-2 appeared in part to be IL-1 dependent. Similarly, low levels of prostaglandin E2 were measured in IL-18-stimulated A549 cells and freshly obtained primary human monocytes and mouse macrophages. We conclude that in epithelial cells, IL-18 signal transduction is primarily via the MAPK p38 pathway rather than NF-kappaB, which may explain the absence of COX-2 and the failure of IL-18 to cause fever.
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PMID:Differences in signaling pathways by IL-1beta and IL-18. 1516 79

The aims of this study were (1) to correlate cough and body temperature (BT) with the severity of bronchopneumonia in pigs, (2) to determine whether these clinical signs can be used to early diagnose bronchopneumonia and (3) to assess the predictive values of cough and BT regarding lung lesions. Bronchopneumonia was induced by administering E. coli endotoxin (LPS) combined with Pasteurella multocida type A (PmA) in the trachea of 13 piglets. Saline-instilled negative controls (n = 8), PmA inoculated (n = 6) and LPS instilled (n = 5) groups were also constituted. Cough and BT were recorded daily while the bronchopneumonia severity was assessed using bronchoalveolar lavage fluid (BALF) cytology, cytokines and measurement of lung lesion volume. Changes in expiratory breathing pattern were also measured (Penh). The combination of LPS and PmA induced a subacute bronchopneumonia characterised by macrophage, neutrophil, and lymphocyte infiltration, changes in Penh and an increase in the mRNA level of IFN-gamma while IL8, IL-18 and TNF-alpha mRNA levels remained unchanged. The daily body weight gain of infected animals was significantly reduced. Cough and BT changes were proportional to the intensity of the lung inflammatory process, functional respiratory changes and to the extent of macroscopic lesions. When comparing the individual values of cough and BT to thresholds defined for both parameters, an early diagnosis of pneumonia was possible. Considering the pooled data of each group, it was possible to define thresholds allowing an early segregation between the groups of diseased and healthy piglets. The daily values of cough and BT were predictive for the volume of lung lesions recorded at the end of the trial. In conclusion, cough and BT appear as potential indicators for the intensity and the evolution of the respiratory disease. They also seem to be good predictors for the magnitude of lung lesions and weight gain recorded at the study endpoint.
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PMID:Pathophysiological changes occurring during Escherichia coli endotoxin and Pasteurella multocida challenge in piglets: relationship with cough and temperature and predicitive value for intensity of lesions. 1521 80

Mucosal surfaces represent the entry route of a multitude of viral pathogens. For many of these viruses, such as the herpes simplex viruses and human immunodeficiency virus, no effective vaccine exists. Hence, it is important that prospective vaccines engender maximal immunity at these susceptible sites. Genetic vaccines encoding adjuvant molecules represent one approach to optimize mucosal as well as systemic immunity. Promising candidates include various inflammatory cytokines and chemokines that might be used to enhance the primary response to a level sufficient for protection. Encouraging studies involving cytokines such as granulocyte/macrophage colony-stimulating factor, interleukin-2 (IL-2), IL-12, IL-18, and many others are examined. Notable chemokines that may offer hope in such efforts include IL-8, RANTES, CCL19, CCL21, and a few others. Combinatorial approaches utilizing several cytokines and chemokines will most likely yield the greatest success. In addition, as more is discovered regarding the requirements for memory development of T cells, boosters involving key cytokines such as IL-15 and IL-23 may prove beneficial to long-term maintenance of the memory pool. This review summarizes the progress in the use of genetic vaccines to achieve mucosal immunity and discusses the needed strategies to maximize long-term prospective immunity at this vulnerable entry site.
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PMID:Molecular adjuvants for mucosal immunity. 1523 29


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