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)

We have previously shown that lymphocytes from idiopathic minimal-lesion nephrotic patients produce a lymphokine (supernatant factor) that increases the 35sulfate uptake in the glomerular basement membrane (GBM). The purpose of this report was to further characterize the supernatant factor by studying the effects of interleukins (IL) 2-4, 6, and 8, granulocyte-macrophage colony stimulating factor, and tumor necrosis factor on the 35sulfate incorporation by rat glomeruli in vitro. A significant increase in GBM 35sulfate uptake was only seen when the glomeruli were cultured with the addition of IL-8 as compared with control cultures: 10.8 +/- (SEM) 1.7 and 7.9 +/- 1.4 cpm/micrograms GBM protein, respectively (p < 0.005). IL-8 reproduces the effect of the reported supernatant factor on the GBM 35sulfate uptake. Because IL-8 was detected in the supernatant of peripheral mononuclear cell cultures from idiopathic minimal-lesion nephrotic syndrome patients in relapse and because the increased GBM 35sulfate incorporation induced by the supernatant factor has been abolished by the addition to the culture media of anti-IL-8 neutralizing antibodies, we postulate that IL-8 is the previously described supernatant factor.
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PMID:Effect of lymphokines on 35sulfate uptake by the glomerular basement membrane. 858 25

Endothelial cells are critical elements in the evolution of all types of cutaneous inflammation. They participate the pathological process through the synthesis and secretion of pro-inflammatory cytokines, including interleukin 1 (IL1), IL6, IL8, and the three colony stimulating factors G-CSF, M-CSF, and GM-CSF and the two chemotactic factors gro-alpha and MCP. They also express a series of cell-surface proteins and glycoproteins known as cell adhesion molecules that allow circulating leukocytes to selectively bind to endothelial cells. In this paper we discuss the role of endothelial cells in the evolution of cutaneous necrotizing vasculitis, an immunologically mediated clinical disorder associated with segmental inflammation and fibrinoid necrosis of the dermal venules, through the release of cytokines or their response to cytokines locally produced from leukocytes themselves primarily involved in the endothelial cells injury. This interaction seems to involve and modulate other biologically active systems including the fibrinolytic system that can act amplifying and self-perpetuating the tissue damage through a non-immunologic mechanism.
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PMID:Cytokines, fibrinolysis and vasculitis. 860 38

Immune globulin for intravenous use (IVIG) has been used in many inflammatory conditions due to its immunomodulatory potential. The effector mechanisms are incompletely understood. This study dealt with the effects of IVIG on cytokine production in vitro. Cytokine synthesis was identified at the single-cell level using cytokine-specific MAb and indirect immunocytochemical techniques. Peripheral blood mononuclear cells (PBMC) were stimulated for 96 h by immobilized anti-CD3 MAb or by a combination of a protein kinase C activator (PMA) and a calcium ionophore (ionomycin). The addition of IVIG (6 mg/ml) caused a marked inhibition of proliferation and blast transformation despite unaffected cell survival. Anti-CD3-stimulated cultures containing IVIG exhibited a significant inhibition of production of T-cell derived lymphokines IL-2, IL-10, TNF-beta, IFN-gamma and TNF-alpha (made by both monocytes and T cells), while synthesis of the monokine IL-8 was significantly increased. The expression of IL-2 receptors was significantly suppressed. Similar but transient inhibition of most T-cell products (IL-2, IL-3, IL-4, IL-5, IL-10, TNF-beta and GM-CSF) was noted in the PMA/ionomycin-containing cultures. In contrast, no effects were found on IFN-gamma or TNF-alpha production. The superantigen streptococcal pyrogenic exotoxin-A (SPE-A) induced vigorous cell activation and extensive cytokine synthesis. IVIG was added either at the beginning or 24 h after the initiation of cultures in order to elucidate the importance of direct toxin-neutralization. Addition of IVIG from the beginning of cultures induced a strong reduction of blast transformation and an almost complete inhibition of lymphokine production, in particular of IFN-gamma and TNF-beta. Supplementation with IVIG 24 h after initiation of cultures also led to a significant decrease in lymphokine synthesis. Monokine production (IL-1 alpha, IL-1 beta, IL-1ra, IL-6 and IL-8) was either unaffected or even increased. These two facts argue against direct antigen-neutralization as being the only mechanism at work. However, in IVIG-exposed PBMC stimulated with LPS, IL-6 production was significantly reduced. A significant upregulation of IL-1ra was noticed in unstimulated PBMC cultured with IVIG. The results in all the experiments did not indicate a cytotoxic effect by IVIG on cell survival and the production of certain cytokines were unaffected. Instead, the authors believe that the results suggest a previously little examined functional link where the humoral immune response may have direct immunoregulatory effects on the cellular immune system.
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PMID:Intravenous immune globulin affects cytokine production in T lymphocytes and monocytes/macrophages. 862 37

A specific receptor for interleukin-8 has been identified on the surface of human monocytes using 125I IL-8 as a probe. A binding kinetic pattern shows that saturation was attained after 90 min and that the receptor was distinct from the receptors of other cytokines (IL-L alpha, IL-2, TNF alpha, GMCSF) and FMLP. Scatchard analysis of the binding data shows that 7000-10,000 receptors /monocyte are present with an equilibrium Kd 7 x 10(-9) M. By immunoblot, the receptor for IL-8 showed a sharp band with approximate M.W. 59 kD, consistent with the M.W. of IL-8 receptor of neutrophils. In Boyden Chamber, monocytes migrated towards IL-8 and the cytokine was observed to induce transient rise of intracellular Ca+2 in the cells. Thus, identification of functionally active IL-8 receptor in monocyte may be helpful for understanding its possible role during inflammation.
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PMID:Identification and characterization of specific receptor for interleukin-8 from the surface of human monocytes. 863 11

Granulocyte colony-stimulating factor (G-CSF) was administered at a dose of 7.5 or 10 micrograms/kg s.c. once daily for 6d (days 1-6) to two groups consisting of eight and six healthy volunteers. The administration of G-CSF resulted in a rapid decrease in neutrophil counts and serum levels of the secondary granule protein, human neutrophil lipocalin (HNL) after 30 min, followed by a recovery and gradual increase within 180 min. The number of circulating neutrophils and plasma and serum levels of neutrophil secondary granule proteins were dramatically elevated on day 2 (1 d after the administration of G-CSF) and stayed so until day 7. The plasma levels of HNL and lactoferrin (LF) showed a biphasic pattern with peaks at day 2 and days 5-7, and remained highly elevated at day 12. The serum levels of HNL and LF increased rapidly (about 8-fold and 6-fold, respectively) on day 2 and stayed elevated until day 7, subsequently returning to baseline levels. At day 5, neutrophil release induced in vitro by f-MLP was significantly enhanced. The cellular contents of HNL and LF were reduced to about 50% of levels before G-CSF administration at day 5. The release of lactoferrin and HNL, but not of myeloperoxidase (MPO), was slightly enhanced after preincubation of isolated normal neutrophils with G-CSF in vitro, but no obvious release of these proteins was observed with G-CSF alone. The administration of G-CSF resulted in a dramatic increase in the alkaline phosphatase (AP) activity in the plasma membrane, with maximal activity occurring at day 5. Furthermore, during administration of G-CSF, TNF-alpha in plasma increased about 25-fold. TNF-alpha started to rise at day 2 and peaked at day 6. After discontinuation of G-CSF the levels of TNF-alpha gradually decreased. The elevated levels of TNF-alpha (tumour necrosis factor-alpha) were temporally correlated to the other signs of neutrophil activation. GM-CSF and IL-8, however, were not detected in plasma. Our data suggest that G-CSF affects the neutrophils not only directly but also indirectly by the induction of the production of other cytokines such as TNF-alpha.
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PMID:The effect of granulocyte colony-stimulating factor (G-CSF) on the degranulation of secondary granule proteins from human neutrophils in vivo may be indirect. 865 73

Macrophage-stimulating protein (MSP), originally identified as an inducer of murine resident macrophage responsiveness to chemoattractants, is a ligand for human RON/murine STK receptor protein tyrosine kinases. Since STK was cloned from populations enriched for hematopoietic stem cells, we initiated studies on the effects of MSP on colony formation by granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) myeloid progenitor cells. MSP alone had no colony stimulating activity. However, MSP caused about a 50% suppression of CFU-GM colony formation induced by synergistic combinations of SLF or Flt-L plus GM-CSF, G-CSF, or IL-3 and of BFU-E and CFU-GEMM colonies induced by SLF or Flt3-L plus Epo or Epo and IL-3. In contrast, MSP had no effect on progenitors stimulated by one growth factor. MSP also suppressed colony formation by stimulated cord blood progenitors, but only after preinduction to a rapidly cycling state. It was previously reported that several members of the chemokine family synergistically suppress myeloid progenitor proliferation. Likewise, synergistic suppression was observed when MSP was paired with VEGF, MIP-1 alpha, IL-8, PF4, MCP-1, IP-10, or ENA-78, or when VEGF was paired with the chemokines; and the required MSP concentration was more than 100-fold less than for MSP alone. Additionally, MSP or VEGF inhibited proliferation of the human myeloid growth factor-dependent cell line, M07e, but a sustained effect required multiple additions over time. At the least, some of the MSP suppressive effects on myeloid progenitors, as assessed on single isolated CD34 marrow cells, appeared to be directly on the progenitors; sustained additions of MSP were required to see this effect. The suppressive action of MSP and its synergism with proteins of the chemokine family may be of relevance to regulation of blood cell production.
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PMID:Macrophage-stimulating protein, a ligand for the RON receptor protein tyrosine kinase, suppresses myeloid progenitor cell proliferation and synergizes with vascular endothelial cell growth factor and members of the chemokine family. 869 17

Analysis of cytokine mRNA and protein in rheumatoid arthritis tissue revealed that many proinflammatory cytokines such as TNF alpha, IL-1, IL-6, GM-CSF, and chemokines such as IL-8 are abundant in all patients regardless of therapy. This is compensated to some degree by the increased production of anti-inflammatory cytokines such as IL-10 and TGF beta and cytokine inhibitors such as IL-1ra and soluble TNF-R. However, this upregulation in homeostatic regulatory mechanisms is not sufficient as these are unable to neutralize all the TNF alpha and IL-1 produced. In rheumatoid joint cell cultures that spontaneously produce IL-1, TNF alpha was the major dominant regulator of IL-1. Subsequently, other proinflammatory cytokines were also inhibited if TNF alpha was neutralized, leading to the new concept that the proinflammatory cytokines were linked in a network with TNF alpha at its apex. This led to the hypothesis that TNF alpha was of major importance in rheumatoid arthritis and was a therapeutic target. This hypothesis has been successfully tested in animal models, of, for example, collagen-induced arthritis, and these studies have provided the rationale for clinical trials of anti-TNF alpha therapy in patients with long-standing rheumatoid arthritis. Several clinical trials using a chimeric anti-TNF alpha antibody have shown marked clinical benefit, verifying the hypothesis that TNF alpha is of major importance in rheumatoid arthritis. Retreatment studies have also shown benefit in repeated relapses, indicating that the disease remains TNF alpha dependent. Overall these studies demonstrate that analysis of cytokine expression and regulation may yield effective therapeutic targets in inflammatory disease.
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PMID:Role of cytokines in rheumatoid arthritis. 871 20

Human fetal thymic epithelial cells (TEC) were cultured under serum-free conditions. The TEC were analyzed for the secretion of 14C-labelled peptides and of IL-3, IL-6 IL-7, IL-8, GM-CSF, LIF, fibronectin and thymosin alpha 1 by ELISA tests. IL-3 and IL-7 were not detected from these TEC. Lack of IL-7 and presence of thymosin alpha 1 and of the surface molecule TE-4 depicts these cells as subcapsular/medullary TEC. TEC secreted constitutively IL-6, IL-8, fibronectin and thymosin alpha 1 but not GM-CSF of LIF. Stimulants included recombinant IL-1 and monoclonal antibodies to the surface adhesion molecules ICAM-1 and LAF-3. In addition, hydrocortisone (2.7 x 10(-7) M) was used to dissect secretion patterns. Recombinant IL-1, anti ICAM-1, and anti LFA-3 alone and collectively induced modest but significant increases in the secretions of 14C-labelled peptides and of IL-6 and IL-8 which were not inhibited by HC. Recombinant IL-1 but not anti ICAM-1 and anti LFA-3 induced GM-CSF and LIF. HC inhibited the secretion of GM-CSF and LIF induced by IL-1. None of the stimulants augmented the constitutive secretion of fibronectin or thymosin alpha 1 and HC inhibited thymosin alpha 1 secretion. TEC secretion of cytokines but not thymosin alpha 1 and fibronectin appear to be regulated in a more complex manner than heretofore recognized.
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PMID:IL-1, ICAM-1, LFA-3, and hydrocortisone differentially regulate cytokine secretion by human fetal thymic epithelial cells. 872 54

Human polymorphonuclear neutrophils (PMN) and cytokines play a critical role in host defences against invading microorganisms. In response to a variety of stimuli, PMN are a major source of reactive oxygen species (ROS) which are essential for bacterial killing and may induce oxidative stress in tissue environment. A precise regulation of the oxidase activity is therefore necessary. Cytokines such as TNF alpha, GM-CSF, IL-8, IL-6, IL-1 alpha and IL-1 beta produced during the immune and inflammatory responses to pathogens have been reported to interact with PMN activities. However, contradictory results have been reported on their direct and priming effects on the PMN release of ROS (oxidative burst). We have used a flow cytometry method to study the effects of these cytokines on the oxidative burst of PMN in whole blood, in order to avoid PMN activation related to isolation procedures. None of the cytokines tested directly activated the PMN oxidative burst, but they did have differential priming effects on the oxidative burst in response to N-formyl peptides. TNF, GM-CSF and IL-8 strongly primed a subpopulation of PMN to produce H2O2 in response to fMLP, while IL-1 alpha, IL-1 beta and IL-6 failed to do so. Furthermore, the addition of TNF, GM-CSF or IL-8 to whole blood increased the capacity of a subpopulation of PMN to bind N-formyl peptides, a phenomenon that could account for the strong H2O2 production in response to fMLP following priming by the cytokines. These results show that, among the various cytokines tested, TNF, GM-CSF and IL-8 strongly prime the PMN oxidative burst in response to bacterial peptides in whole blood and suggest that these cytokines may play a critical role in bacterial killing in vivo and also in the surrounding tissue injury secondary to pathological inflammatory reactions. In particular, TNF and IL-8 plasma levels as well as LPS-induced monocytic production of these cytokines ex vivo have been correlated with the production of ROS by stimulated PMN and with the lung injury score in patients with Adult Respiratory Distress Syndrom (ARDS). However, desensitization phenomena have also been described. In particular, in HIV infected patients we demonstrated a decrease of H2O2 production by PMN in whole blood after ex vivo priming by IL-8 and TNF followed by fMLP stimulation. This decrease increased with the progression of the disease and was inversely correlated with IL-8 plasma level. Different mechanisms could explain such desensitization phenomena at the receptor and post receptor level. In addition cytokines are involved in a complex network of regulation and anti inflammatory cytokines, such as IL-10, could act as a negative signal on the proinflammatory cytokines induced-priming of oxidative burst.
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PMID:[Modulation of the oxidative burst of human neutrophils by pro- and anti-inflammatory cytokines]. 873 98

We examined the mRNA levels for various cytokines, including IL-1 alpha, IL-1 beta, TNF alpha, TGF-beta 1, GM-CSF, IL-6, IL-8, bFGF, PDGF-A, PDGF-B and IL-1ra, and IL-1 beta converting enzyme, and the protein levels of some of these cytokines in 19 SV40-transformed synovial cell clones. Among those tested, the mRNA levels for IL-6, bFGF and PDGF-A in rheumatoid arthritis (RA) cell clones were greater than those in non-RA cell clones. Moreover, except for one osteoarthritis (OA) cell clone, the mRNA levels for IL-8 in RA cell clones were also greater than those in non-RA cell clones. Although the protein levels were not always correlated with the mRNA levels, the exception being the same OA cell clone, the protein levels of cytokines, such as IL-1 alpha, IL-1 beta, IL-6 and IL-8, in RA cell clones were greater than those in non-RA cell clones. TNF-a was not detected in any cells tested at either the mRNA or the protein level. TNF-alpha upregulated the expression of GM-CSF mRNA in both RA cell clones and one OA cell clone, but not in the other OA cell clone or the normal cell clone. Taken together, these SV-40 transformed synovial cell clones retained many of the original characteristics in terms of cytokine production.
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PMID:Cytokine production by SV40-transformed adherent synovial cells from rheumatoid arthritis patients. 874 72


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