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)

Human tumors can constitutively express cytokines and growth factors, but the extent of this expression has not been investigated. Using 44 different probes to cytokines, growth factors, and their receptors, we tested 21 melanoma and 5 melanocyte cultures for RNA transcript expression by reverse transcriptase-polymerase chain reaction. With 30 amplification cycles, expression of the cytokines interleukin (IL)-1 beta, IL-6, leukemia inhibitory factor (LIF), IL-7, gro alpha, IL-8 and the p35 chain of IL-12 was detected in more than 60% of melanomas. Concomitant receptors for IL-6 and IL-7 were also detected. IL-1 alpha, IL-5, Rantes, IL-10, interferon (IFN)-beta, tumor-necrosis factor (TNF)-alpha, G-colony-stimulating factor (CSF) and GM-CSF were expressed at lower levels. Melanocytes showed greatly reduced cytokine RNA transcripts, and only gro alpha was consistently detected. No expression of IL-2, IL-3, IL-4, IL-9, the p40 chain of IL-12, IFN-alpha or IFN-gamma RNA transcripts was detected in melanomas or melanocytes. The growth factors expressed by melanomas and, after further signal amplification, by melanocytes were transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), TGF-beta, endothelial-cell growth factor (ECGF), basic-fibroblast growth factor (bFGF), nerve growth factor (NGF) and steel. The receptors EGFR, FGFR, NGFRp70 and c-kit were also expressed by melanomas and melanocytes. These results point to new possible autocrine and paracrine pathways in melanoma biology.
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PMID:Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes. 750 78

Recently, we described the cloning and expression of a human cDNA which is the homologue to P600, a gene transcribed by mouse Th2 clones. Based on its activities on human monocytes and B cells this gene was designated IL-13. In the present study we investigated the effects of IL-13 alone or in combination with IL-4, IFN-gamma, or IL-10 on human monocytes. IL-13 induced significant changes in the phenotype of monocytes. Like IL-4, it enhanced the expression of CD11b, CD11c, CD18, CD29, CD49e (VLA-5), class II MHC, CD13, and CD23, whereas it decreased the expression of CD64, CD32, CD16, and CD14 in a dose-dependent manner. IL-13 induced up-regulation of class II MHC Ag and its down-regulatory effects on CD64, CD32, and CD16 expression were prevented by IL-10. IFN-gamma could also partially prevent the IL-13-induced down-regulation of CD64, but not that of CD32 and CD16. However, IL-13 strongly inhibited spontaneous and IL-10- or IFN-gamma-induced ADCC activity of human monocytes toward anti-D coated Rh+ erythrocytes, indicating that the cytotoxic activity of monocytes was inhibited. Furthermore, IL-13 inhibited production of IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, IL-12 p35, IL-12 p40, macrophage inflammatory protein-1 alpha, granulocyte/macrophage-CSF, granulocyte-CSF, IFN-alpha, and TNF alpha by monocytes activated with LPS. In contrast, IL-13 enhanced the production of IL-1 ra by these cells. Similar results on cytokine production were observed or have been obtained with IL-4. Thus IL-13 shares most of its activities on human monocytes with IL-4, but no additive or synergistic effects of IL-4 and IL-13 on human monocytes were observed, suggesting that these cytokines may share common receptor components. Taken together, these results indicate that IL-13 has anti-inflammatory and important immunoregulatory activities.
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PMID:Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. 790 77

Interleukin (IL)-12 is thought to be a key factor for the induction of interferon gamma (IFN-gamma), a cytokine essential for the lethal effects of endotoxin. We report here on the release of the nonfunctional subunit of IL-12, p40, as well as biologically active heterodimeric IL-12, p70, after administration of a lethal (n = 5) or sublethal (n = 8) dose of live Escherichia coli to baboons. Remarkably, on lethal challenge, peak levels of p40 were observed at 3 hours that were about twofold lower than those elicited after sublethal challenge (2,813 +/- 515 pg/mL v 4,972 +/- 732 pg/mL, P < .05). This disparity was also observed, although to a lesser extent, for IL-12 p70 antigen, of which maximum levels of 91 +/- 47 pg/mL and 151 +/- 41 pg/mL were measured 6 hours after a lethal or sublethal dose of E coli, respectively. Circulating p70 antigen correlated with IL-12 biologic activity (r = 0.869; P < .001). When comparing lethal to sublethal conditions, lower peak levels of IL-12 on lethal E coli sharply contrasted with higher levels of other proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6, and IL-8 observed in these animals. Lower IL-12 concentrations in the lethal group may have resulted in part from the enhanced production of IL-10, a known inhibitor of IL-12 synthesis in vitro, as peak levels of this cytokine 3 hours postchallenge inversely correlated with peak levels of IL-12, in particular p40 (r = -0.802; P < .01). Contrary to what might be expected if IFN-gamma were solely induced by IL-12, lethally challenged baboons generated threefold more IFN-gamma at 6 hours than those receiving a sublethal dose (P < .05). Moreover, higher levels of IFN-gamma were associated with lower p40/p70 ratios, suggesting that, in agreement with observations in vitro, IFN-gamma may have preferentially upregulated the release of p70 over p40. These data show that IL-12 is released in experimental septic shock in nonhuman primates and suggest that IL-10 and IFN-gamma are involved in the regulation of this release. Furthermore, this study indicates that the systemic release of IL-12 might be essential, but is not likely sufficient, to promote lethal production of IFN-gamma in sepsis.
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PMID:Release of interleukin-12 in experimental Escherichia coli septic shock in baboons: relation to plasma levels of interleukin-10 and interferon-gamma. 865 27

To assess the role of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in children with bacterial meningitis, bioactive IL-12 (p70) and the inactive subunit p40 and IFN-gamma were measured in serum and cerebrospinal fluid (CSF) from 35 children with bacterial meningitis and 10 control subjects. The production of IFN-gamma is induced by IL-12 with tumor necrosis factor alpha (TNF-alpha) as a costimulator and inhibited by IL-10. CSF concentrations of IL-12 p40 as well as those of IFN-gamma were markedly elevated, whereas IL-12 p70 was hardly detectable. Detectable CSF levels of IFN-gamma correlated positively with IL-12 p40 (r = 0.40, P = 0.02) and TNF-alpha (r = 0.46, P = 0.04) but not with IL-6, IL-8, or IL-10. In contrast to CSF levels of TNF-alpha, IL-12, and IL-10, those of IFN-gamma were significantly higher in patients with pneumococcal meningitis than in children with meningitis caused by Haemophilus influenzae and Neisseria meningitidis, presumably because of a high CSF TNF-alpha/IL-10 ratio in the former. We suggest that IL-12- and TNF-alpha-induced IFN-gamma production may contribute to the natural immunity against microorganisms in the CSF compartment during the acute phase of bacterial meningitis.
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PMID:Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis. 903 91

IL-12 is a heterodimeric cytokine produced by phagocytic and other cells with important physiologic and pathologic properties. Regulated IL-12 production is crucial for the generation of protective Th1 responses to infectious agents. In contrast, IL-12 excess contributes to the pathogenesis of a variety of autoimmune and inflammatory disorders. To further understand the processes regulating IL-12 production, we determined whether IL-11 regulated monocyte/macrophage production of this cytokine moiety. IL-11 did not alter the IL-12 (p70) production of unstimulated THP-1 monocytic cells or human blood monocytes. It did, however, inhibit, in a dose-dependent fashion, the IL-12 production of IFN-gamma plus Staphylococcus aureus Cowan strain 1-stimulated THP-1 cells and stimulated blood monocytes. This inhibition of IL-12 protein production was associated with a proportionate decrease in IL-12 p35 and p40 mRNA accumulation. Nuclear run-on assays revealed comparable decreases in IL-12 p35 and p40 gene transcription. IL-11 did not similarly regulate monocyte/macrophage production of IL-8 or macrophage inflammatory protein-1alpha (MIP-1alpha) and IL-6 did not similarly inhibit IL-12 elaboration. These studies demonstrate that IL-11 is a potent inhibitor of monocyte/macrophage IL-12 production and that this inhibitory effect is, at least in part, transcriptionally mediated. They also demonstrate that this inhibition is not the result of a generalized suppression of macrophage effector function and that the ability to inhibit monocyte/macrophage IL-12 production is not a generalized property of all IL-6-type cytokines.
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PMID:Interleukin-11 inhibits macrophage interleukin-12 production. 927 3

Fc gamma RIII (CD16), a low affinity FcR which binds IgG-containing immune-complexes, exists under membrane-associated forms and under a soluble form (sFc gamma RIII). The latter, present in biological fluids (serum, saliva), is generated by proteolytic cleavage of the two membrane-associated Fc gamma RIII isoforms, Fc gamma RIII-A (expressed by macrophages and NK cells) and Fc gamma RIII-B (expressed exclusively by neutrophils). Herein we demonstrate that dendritic cells (DCs), generated by culturing monocytes with GM-CSF and IL-4, bind biotinylated recombinant sFc gamma RIII. This binding is specific and involves the complement receptor CR3 (CD11b/CD18) and CR4 (CD11c/CD18). Indeed, preincubation of DCs with anti-CD11b and anti-CD11c mAbs decreased by 52% and 62% respectively the binding with sFc gamma RIII. Moreover, electron microscopy showed that binding of gold-labeled sFc gamma RIII to DCs maintained at 4 degrees C occurred within clathrin-coated pits. Once internalized, at 37 degrees C, sFc gamma RIII entered the endocytic pathway and reached the MHC class II compartments. Furthermore, DCs incubated for 48 h with multivalent sFc gamma RIII expressed increased levels of CD40, CD80, CD86, CD54, CD58, HLA class I and class II molecules and decreased levels of CD23 and CD32. These effects result in an increased capacity of DCs to trigger proliferative responses by CD4+ CD45RA+ allogeneic T cells. RT-PCR amplification demonstrated that incubation of DCs for 20 h in the presence of multivalent sFc gamma RIII induced the appearance of GM-CSF and IL-12 p40 mRNA. Among the cytokines constitutively expressed, IL-1 beta and IL-8 were strongly up-regulated whereas IL-6 and IL-12 p35 mRNA were increased to a lesser extent and the expression of MIP-1 alpha mRNA remained constant. Finally, ELISA tests demonstrated that DCs incubated with multivalent sFc gamma RIII secreted the cytokines IL-1 beta, IL-6, IL-8, GM-CSF and IL-12 p75. Thus, while becoming internalized sFc gamma RIII could affect the capacity of DCs to present antigens and, via the induction of accessory molecules and the release of the IL-12 p75 protein, could initiate Th1 type immune response.
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PMID:Soluble CD16/Fc gamma RIII induces maturation of dendritic cells and production of several cytokines including IL-12. 928 84

Cytokines play an important role in granuloma formation, but the extent that cytokine profiles are similar in different granulomatous diseases and whether differences in the histopathologic features of the granulomatous response results from differences in cytokine production have not been evaluated. To investigate these questions, we used RT-PCR to quantify the expression of mRNAs coding for 16 cytokines in granulomatous lymph nodes from patients with tuberculosis and sarcoidosis and from control tissues, and we sought correlations between the level of expression of these cytokines and the histopathologic features of the granulomas. Expression of mRNAs coding for a number of cytokines (IL-1beta, IFN-gamma, TNF-alpha, granulocyte-macrophage (GM)-CSF, IL-12 (p40), and lymphotoxin-beta) was increased in tuberculous and sarcoid granulomas compared with that of control tissues. All sarcoid granulomas were shown to express a Th1 pattern of cytokine mRNAs, while tuberculous lymph nodes expressed either a Th1 or a Th0 profile. GM-CSF and lymphotoxin-beta mRNAs were more abundant in sarcoid than in tuberculous granulomas, whereas IL-8 mRNA was strongly expressed only in tuberculous lymph nodes. Strong expression of GM-CSF, TNF-alpha, and IL-8 by granulomas was shown to be correlated, respectively, with the presence of florid granulomatous lesions, the absence of central necrosis, and the presence of neutrophil infiltration. These results demonstrate that the formation of tuberculous and sarcoid granulomas in humans is associated with the expression of characteristic cytokine profiles and indicate that the expression of certain cytokines is associated with the development of specific pathologic features in the resulting granulomas.
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PMID:Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response. 930 Jul 29

Caprine arthritis encephalitis virus (CAEV) is a lentivirus of goats that leads to chronic mononuclear infiltration of various tissues, in particular, the radiocarpal joints. Cells of the monocyte/macrophage lineage are the major host cells of CAEV in vivo. We have shown that infection of cultured goat macrophages with CAEV results in an alteration of cytokine expression in vitro. Constitutive expression of interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) was increased in infected macrophages, whereas transforming growth factor beta1 (TGF-beta1) mRNA was down-regulated. When macrophages were infected with a CAEV clone lacking the trans-acting nuclear regulatory gene tat, IL-8 and MCP-1 were also increased. No significant differences from cells infected with the wild-type clone were observed, suggesting that Tat is not required for the increased expression of IL-8 and MCP-1 in infected macrophages. Furthermore, infection with CAEV led to an altered pattern of cytokine expression in response to lipopolysaccharide (LPS), heat-killed Listeria monocytogenes plus gamma interferon, or fixed cells of Staphylococcus aureus Cowan I. In infected macrophages, tumor necrosis factor alpha, IL-1beta, IL-6, and IL-12 p40 mRNA expression was reduced in response to all stimuli tested whereas changes in expression of granulocyte-macrophage colony-stimulating factor depended on the stimulating agent. Electrophoretic mobility shift assays demonstrated that, in contrast to effects of human immunodeficiency virus infection of macrophages, CAEV infection had no effect on the level of constitutive nuclear factor-kappaB (NF-kappaB) activity or on the level of LPS-stimulated NF-kappaB activity, suggesting that NF-kappaB is not involved in altered regulation of cytokine expression in CAEV-infected cells. In contrast, activator protein 1 (AP-1) binding activity was decreased in infected macrophages. These data show that CAEV infection may result in a dysregulation of expression of cytokines in macrophages. This finding suggests that CAEV may modulate the accessory functions of infected macrophages and the antiviral immune response in vivo.
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PMID:Caprine arthritis encephalitis virus dysregulates the expression of cytokines in macrophages. 931 28

Plasma levels of interleukin 12 (IL-12), a cytokine consisting of two different polypeptide subunits (p40 and p35), were measured together with interferon gamma (IFN-gamma) and other cytokines in 46 children with septic shock and purpura. The median (range) plasma IL-12 p40 level on admission was 457 (244-2677) pg/ml in non-survivors vs 189 (< 40-521) pg/ml in survivors (P = < 0.001). IL-12 p70 levels were elevated in only nine patients. IL-12 p40 plasma levels were positively correlated with tumour necrosis factor alpha (TNF-alpha), IL-6, IL-8, IL-10 and PRISM-score, whereas they were negatively correlated with C-reactive protein (CRP), whole blood cell (WBC) and serum glucose levels. Twelve (29%) of the patients had detectable levels of IFN-gamma. Thus, circulating levels of IL-12 p40 and to a lesser extent those of IL-12 p70, are elevated in children with septic shock and purpura, and correlate with severity of disease and outcome.
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PMID:Interleukin 12 levels during the initial phase of septic shock with purpura in children: relation to severity of disease. 932 21

Cytokines are signalling glycoproteins mediating acute inflammation, chronic inflammation, and connective tissue destruction. The present study was designed to characterize the profile of cytokine message in normal human articular cartilage and from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), by means of the reverse transcriptase-polymerase chain reaction (RT-PCR). Message RNA (mRNA) was extracted from fresh or frozen cartilage. The results showed expression of mRNA for IL-6, IL-6R, IL-7, IL-8, IL-10, and IL-12 (p35 and p40) exclusively in the RA cartilage. Except for mRNA for IL-8 and IL-10, no other cytokine or cytokine receptor was expressed in OA and control cartilage. mRNA for IL-1beta, IL-4, TNF-alpha, and TNFR-p75, was not detected in any cartilage sample except for one RA specimen expressing IL-1beta mRNA. However, the expression of message for pro-inflammatory cytokines was far more prominent than anti-inflammatory cytokines. This may suggest a disturbed balance of pro- and anti-inflammatory activity in RA cartilage.
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PMID:Detection of cytokine mRNA in human, articular cartilage from patients with rheumatoid arthritis and osteoarthritis by reverse transcriptase-polymerase chain reaction. 950 80


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