UNIPROT:P10145 - FACTA Search

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)

Interleukin-8 (IL-8) has at least two binding regions for both the A and the B type IL-8 receptors. This study defines an important region between Cys7 and Cys50 that, together with the Glu4-Leu5-Arg6 sequence of the NH2 terminus, accounts for the high affinity binding of IL-8 to the IL-8 A receptor on leukocytes. Utilizing rabbit IL-8 that shares 82% sequence identity with human IL-8, but has 200-fold lower binding affinity for the IL-8 A receptor, residues of the human homologue were sequentially exchanged into the rabbit molecule. Replacement of rabbit His13 and Thr15 with Tyr13 and Lys15 of the human molecule converted the low affinity binding of the rabbit IL-8 to the high affinity binding of human IL-8 as shown by both competitive binding and by Ca2+ mobilization. As a corollary, replacement of the Tyr13 and Lys15 of the human IL-8 with His13 and Thr15 of the rabbit IL-8 reduced binding activity of this mutated human IL-8 200-fold. The site of interaction on the IL-8 receptor type A for the Tyr13 and Lys15 sequence was found to be in the NH2-terminal region of this receptor. A structural pattern of the binding between IL-8 and the A type IL-8 receptor is proposed.
...
PMID:The role of Tyr13 and Lys15 of interleukin-8 in the high affinity interaction with the interleukin-8 receptor type A. 773 76

Chronic inflammatory responses in the lung rely on the continual recruitment of leukocytes to the site of inflammation. Recent data have demonstrated a possible role for stromal cell-derived chemokines in leukocyte recruitment. In the present study we examined the production of interleukin (IL)-8 and ENA-78, members of the C-X-C family of chemokines, and macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, members of the C-C chemokine family, from pulmonary smooth muscle and endothelial cells. The production of IL-8 and ENA-78 was induced by early response cytokines, IL-1 and tumor necrosis factor (TNF), but not by immune-associated cytokines, IL-4, IL-10, or interferon (IFN)-gamma. In contrast, the production of MIP-1 alpha and MIP-1 beta by pulmonary vascular smooth muscle cells increased when stimulated by immune-associated cytokines as well as with IL-1 beta and TNF. The level of MIP-1 alpha production induced in smooth muscle cells by the immune-associated cytokines, IL-4, IFN-gamma, and IL-10 ranged from 0 to 340 pg/ml. The production of MIP-1 beta in response to the immune-associated cytokines IL-4, IFN-gamma, and IL-10 in smooth muscle cells ranged from 260 to 940 pg/ml. Human pulmonary artery endothelial cells did not generate MIP-1 alpha or MIP-1 beta in response to graded doses of any of the cytokines. These data demonstrate differential induction of C-X-C and C-C chemokines from nonimmune stromal cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Stimulus and cell-specific expression of C-X-C and C-C chemokines by pulmonary stromal cell populations. 776 89

The arrival of inflammatory phagocytic cells, namely neutrophils and mononuclear phagocytes, in the pleural space is a hallmark of pleural inflammation. It is probable that the temporal arrival of cells is mediated via the release of chemotactic cytokines by activated mesothelial cells. We hypothesized that human pleural mesothelial cells activated by bacterial endotoxin lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), or tumor necrosis factor-alpha (TNF-alpha) release cell-specific chemokines from the C-C and C-X-C family of chemokines, specifically monocyte chemoattractant protein 1 (MCP-1) and IL-8. We evaluated supernatants of stimulated mesothelial cells for biologic chemotactic activity for monocytes and neutrophils and quantitative antigenic protein levels for MCP-1 and IL-8. Expression of the proteins at mRNA level was tested via Northern blot analysis. We found that responses to LPS were significantly higher (P less than 0.05) than control supernatants of unstimulated mesothelial cells. Responses to IL-1 beta and TNF-alpha were significantly greater than those to LPS. Neutralization studies with specific rabbit anti-MCP-1 and IL-1 antibody demonstrated significant decreases in bioactivity for MCP-1 and IL-8, indicating that mesothelial cell-derived MCP-1 and IL-8 play a significant role in the chemotactic activity seen in stimulated mesothelial cell supernatants. On specific enzyme-linked immunosorbent assay testing, stimulated mesothelial cells produced significantly more MCP-1 and IL-8 when stimulated with IL-1 beta or TNF-alpha as compared to LPS. mRNA expression for MCP-1 peaked within 2 to 4 h following stimulation and was noted as early as 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Pleural mesothelial cell expression of C-C (monocyte chemotactic peptide) and C-X-C (interleukin 8) chemokines. 776 22

Under certain physiological and pathological conditions, natural killer (NK) cells rapidly accumulate in tissues. Chemokines are an essential component of the current paradigm of leukocyte recruitment. The present study was designed to investigate the responsiveness of NK cells to the prototypic C-C chemokine, monocyte chemotactic protein-1 (MCP-1). MCP-1 induced migration across filters of interleukin (IL)-2-activated NK cells, whereas it was a weak attractant for unstimulated cells. Maximal induction of migration required a positive concentration gradient between the lower and the upper compartment of the chemotaxis chamber. Preliminary characterization of the MCP-1 receptor on NK cells indicated that the chemotactic response to MCP-1 was blocked by pre-treatment of cells with Bordetella pertussis toxin, and MCP-1 but not IL-8 displaced 125I-labeled MCP-1 from IL-2-activated NK cells. The related chemokines MCP-2 and MCP-3 were also active--though less potent--attractants for activated NK cells. Thus the spectrum of action of MCP-1, -2 and -3 encompasses NK cells and chemokines are likely to play a role in regulating extravasation of these cells.
...
PMID:Induction of natural killer cell migration by monocyte chemotactic protein-1, -2 and -3. 780 52

Interleukin-8 is a member of the chemokine superfamily and is a major mediator of acute inflammation. Although IL-8 has been reported by some laboratories also to be a chemoattractant for T lymphocytes, this has been difficult to confirm and remains a controversial issue. By using freshly purified human T cells (90-95% CD3+), we could demonstrate consistent directional migration of T cells to recombinant human IL-8. IL-8 was as potent as RANTES, MIP1 alpha, and MIP1 beta in inducing T cell chemotaxis. Highly purified T cells, however, incubated at 37 degrees C for more than 12 h or cultured overnight with anti-CD3 antibody cross-linked to plastic dishes, showed a markedly reduced capacity to migrate in response to IL-8. This was associated with a decrease in binding of radioiodinated IL-8 to T cells. Northern blot and polymerase chain reaction analyses showed that freshly purified T cells expressed mRNA for both IL-8 receptor type A and type B. Steady-state levels of mRNA for the IL-8RA and IL-8RB genes were also reduced by incubation of the cells with or without anti-CD3 for 12 h at 37 degrees C. These results indicate that T cells are indeed one of the target cell populations for IL-8. The regulation of IL-8 receptor expression on T lymphocytes may contribute to the pathophysiological role of IL-8 in inducing the homing and infiltration of T cells.
...
PMID:Modulation of IL-8 receptor expression on purified human T lymphocytes is associated with changed chemotactic responses to IL-8. 785 48

Chemokines are a superfamily of structurally related cytokines involved in leukocyte recruitment in normal and neoplastic tissues. The availability of non-cross-reacting reagents specific for each member of the C-C and C-X-C family is important for careful characterization of their in vitro and in vivo production and relevance. Here we describe a novel, highly specific, mAb against monocyte chemotactic protein-1 (MCP-1). The 5D3-F7 mAb (IgG1,kappa) recognizes human recombinant and natural MCP-1 in ELISA, immunoprecipitation and immunoblot analysis. As a source of natural MCP-1 we used the 8387 human sarcoma line which produces spontaneously MCP-1 and responds to TNF with increased expression and release. The 5D3-F7 mAb inhibited the chemotactic activity of MCP-1 for monocytes. Using the 5D3-F7 mAb and a polyclonal rabbit anti-MCP-1 serum, a sandwich ELISA was developed. In both the direct and the sandwich ELISA, the 5D3-F7 mAb recognized human MCP-1, but not the closely related C-C chemokines MCP-1, MCP-2, MCP-3, MIP-1 alpha, and RANTES and the C-X-C chemokines IL-8, gro alpha and NAP-2. In culture supernatants the sensitivity of the sandwich ELISA was approximately equal to 30 pg/ml. The sandwich ELISA permitted detection of MCP-1 in resting or cytokine-stimulated endothelial, mesothelial and Kaposi's sarcoma cells. Preliminary immunohistochemical analysis revealed production of MCP-1 by macrophage-like cells at sites of inflammation. The 5D3-F7 mAb provides a novel, highly specific reagent with which to investigate the in vitro and in vivo production and role of MCP-1.
...
PMID:A new monoclonal antibody (5D3-F7) which recognizes human monocyte-chemotactic protein-1 but not related chemokines. Development of a sandwich ELISA and in situ detection of producing cells. 808 29

We have previously demonstrated that a basic amino acid residue of interleukin (IL)-8, namely Arg-6, is critical for the binding of IL-8 to its receptor. We reasoned that this residue is likely to be poised to directly interact with a counterpart acidic residue on the receptor. To identify this key residue, we systematically mutated to Ala all acidic residues present on the ligand accessible surface of IL-8 receptor type A. Using this strategy, we demonstrate that two residues which are present in extracellular loop 3 of the receptor, namely Glu-275 and Arg-280, are critical for ligand binding. In addition, we show that although Asp-11 is critical for ligand binding, a conservative mutation of Asp-11 to Glu or a substitution of Asp-11 with Lys (the residue found at position 11 in IL-8 receptor type B) does not affect the Kd of the receptor/ligand interaction. These data suggest that Lys-11 recruits a new and favorable interaction with IL-8 (analogous to that of IL-8 receptor type B with IL-8) or that the cavity created by mutating Asp-11 to Ala is particularly deleterious. Finally, we discuss fluorescence-activated cell sorter staining data which support the hypothesis that the N-terminal region and the extracellular loop 3 of the receptor may lie in close proximity of one another and constitute a major binding domain for IL-8.
...
PMID:Partial functional mapping of the human interleukin-8 type A receptor. Identification of a major ligand binding domain. 810 45

In this study, we examined IL-10 regulation of polymorphonuclear leukocyte (PMN)-derived chemokine expression. Studies demonstrated that IL-10 dose dependently suppressed the expression and production of PMN-derived macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, IL-8 mRNA, and protein. Although inhibition of protein synthesis was found to superinduce the expression of PMN-derived chemokine steady-state mRNA, the inhibitory activity of IL-10 was completely abrogated in the presence of either cycloheximide or puromycin. These data suggest that the effect of IL-10 on PMN-derived chemokine expression was through the production of de novo repressor protein(s). Next, we examined the half-life (t1/2) of chemokine mRNA by LPS-treated PMNs in the presence or absence of IL-10. The t1/2 of MIP-1 alpha, MIP-1 beta, and IL-8 mRNA from PMNs treated for 4 h with LPS before actinomycin-D (Ac-D) addition were approximately 40 min, 1.7 h, and 2 h, respectively, whereas the t1/2 from PMNs stimulated for 8 h before Ac-D were 2, 2, and > 9 h, respectively. Interestingly, IL-10 significantly accelerated the decay of all three of the above chemokine mRNA. The t1/2 of MIP-1 alpha, MIP-1 beta, and IL-8 mRNA from PMNs treated with LPS plus IL-10 compared with LPS alone was reduced by 62, 50, and 40%, respectively, at the 4-h time point and by 50, 25, and 70%, respectively, at the 8-h time point. These findings support the notion that PMNs are an important cellular source of both C-X-C and C-C chemokines, and that IL-10 regulates both inflammatory/immune responses by not only modulating the activities of T cell, B cell, and mononuclear phagocyte function, but also by inhibiting PMN-derived chemokine expression.
...
PMID:Regulation of neutrophil-derived chemokine expression by IL-10. 814 35

Previous studies have shown that during the development of a mixed lymphocyte reaction (MLR) levels of the chemotactic cytokines IL-8 and MCP-1 (members of the C-X-C and C-C supergene families, respectively) increase in a time-dependent fashion, and that the production of these chemokines correlates with the magnitude of responsiveness to alloantigen. Furthermore, the responsiveness to alloantigen in the context of a MLR has been shown to be regulated by the oxidative metabolism of L-arginine. We postulated that competitive antagonism of the L-arginine metabolic pathway in a human MLR may alter the production of members of the C-C and C-X-C chemokine families. To test this hypothesis, mononuclear cells were isolated from healthy individuals and subjected to a one-way MLR in the presence or absence of varying concentrations of an L-arginine competitive inhibitor, NG-methyl-L-arginine (NMA: 50 to 500 microM). When the MLR was performed in the presence of NMA (500 microM), the production of IL-8 increased twofold (P < 0.05) and ENA-78 increased fivefold (P < 0.05), while MCP-1 and MIP-1 alpha were not significantly altered. These findings suggest that NMA, an inhibitor of the L-arginine metabolic pathway, may regulate the production of specific C-X-C chemokines, IL-8 and ENA-78, during a MLR. In contrast, the production of MCP-1 and MIP-1 alpha, members of the C-C chemokine family, does not appear to be regulated by this inhibitor of the oxidative metabolism of L-arginine in the context of a MLR.
...
PMID:Regulation of chemokine production by the oxidative metabolism of L-arginine in a human mixed lymphocyte reaction. 820 45

The temporal recruitment of leukocytes to a site of inflammation is dependent on a complex interplay of a number of soluble mediators. Recently, two families of chemotactic cytokines have been discovered. The -C-X-C-family, which includes IL-8, appears to recruit neutrophils and lymphocytes. In contrast, the -C-C-family, which includes monocyte chemotactic peptide-1 (MCP-1), appears to recruit predominantly monocytes. Monocytes, after their arrival at a site of inflammation, could further amplify the immune response by secreting IL-8 and MCP-1. We sought to define conditions under which human peripheral blood monocytes produce IL-8 and MCP-1. Using serum-free media, we found that PHA-stimulated monocytes expressed MCP-1 and IL-8 protein and mRNA in a dose-dependent manner. However, the onset of mRNA expression for MCP-1 occurred at least 3 h later than did the onset of IL-8 mRNA expression. IL-8 and MCP-1 gene expression by monocytes appeared to require de novo protein synthesis, in that cycloheximide blocked the expression of mRNA for both IL-8 and MCP-1 in PHA-stimulated cells. However, treatment of monocytes with cycloheximide resulted in the superinduction of IL-8 compared with control monocytes. Monocytes costimulated with PHA and LPS demonstrated enhanced amounts of IL-8 mRNA and protein, but sharply decreased amounts of MCP-1 mRNA and protein. The addition of serum to culture media increased both the constitutive and PHA-induced production of monocyte-derived MCP-1 and IL-8, but had no effect on the inhibition of PHA-stimulated MCP-1 production by LPS. These findings suggest that distinct pathways of activation exist for the production of monocyte-derived IL-8 and MCP-1. The differential expression of these different but related polypeptides may offer a means of control of the type of immune cells that are recruited to a site of inflammation.
...
PMID:Production of IL-8 and monocyte chemotactic peptide-1 by peripheral blood monocytes. Disparate responses to phytohemagglutinin and lipopolysaccharide. 825 94

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>