Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functions of wild-type and mutant mouse interleukin-10 receptors (mIL-10R) expressed in murine Ba/F3 cells were studied. As observed previously, IL-10 stimulates proliferation of IL-10R-expressing Ba/F3 cells. Accumulation of viable cells in the proliferation assay is to a significant extent balanced by concomitant cell death. Moreover, growth in IL-10 also induces a previously unrecognized response, differentiation of the cells, as evidenced both by formation of large clusters of cells in cultures with IL-10 and by induction or enhancement of expression of several cell surface antigens, including CD32/16, CD2, LECAM-1 (v-selectin), and heat-stable antigen. Two distinct functional regions near the C terminus of the mIL-10R cytoplasmic domain which mediate proliferation were identified; one of these regions also mediates the differentiation response. A third region proximal to the transmembrane domain was identified; removal of this region renders the cell 10- to 100-fold more sensitive to IL-10 in the proliferation assay. In cells expressing both wild-type and mutant IL-10R, stimulation with IL-10 leads to tyrosine phosphorylation of the kinases JAK1 and TYK2 but not JAK2 or JAK3 under the conditions tested.
Mol Cell Biol 1995 Sep
PMID:Functional regions of the mouse interleukin-10 receptor cytoplasmic domain. 754 37

Human lung dendritic cells (DC) are considerably more potent than alveolar macrophages (AM) in inducing allogeneic T-cell proliferation. Tumor necrosis factor (TNF) alpha and beta produced during alloreaction are likely to be major inflammatory cytokines involved. Their concentrations were therefore analyzed during the interaction of AM or DC with allogeneic T cells. TNF alpha and TNF beta levels were respectively three-fold and sevenfold higher in the presence of DC as compared with AM. Cytokines such as interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor beta (TGF beta) were compared as to their ability to control DC-induced T-cell proliferation as well as TNF alpha or TNF beta production. IL-10 had the unique capacity of reducing both TNF alpha and TNF beta production by 60 +/- 5% (mean +/- SEM) and 63 +/- 12%, respectively, while inhibiting T-cell proliferation by only 32 +/- 23%. IL-4 and TGF beta increased the release of TNF beta by 275 +/- 22% and 95 +/- 32%, respectively, while that of TNF alpha was slightly decreased or unchanged. An additive effect of IL-10 to cyclosporine was found for all three parameters studied. Interaction between CD4 or CD8 with DC was affected similarly by IL-10. Part of this effect could be due to the downregulation of class I and class II major histocompatibility complex expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1995 Jul
PMID:Interleukin-10 decreases tumor necrosis factor alpha and beta in alloreactions induced by human lung dendritic cells and macrophages. 759 41

1. Recent data have shown that interleukin-10 (IL-10) is expressed and acts in mouse pituitary tumor cells and freshly isolated mouse pituitaries. 2. In this study, we show that poly(A+) RNA derived from normal human pituitary and hypothalamus expresses IL-10 message. 3. The majority of transcripts was likely from the pituitary and hypothalamus, and not from lymphocytes in the pituitary and hypothalamic vasculature, since both IL-10 and interferon-gamma mRNA levels, compared to equivalent amounts of RNA from peripheral blood lymphocytes, were much lower. 4. These results indicate that IL-10 may function in human neuroendocrine process as it does in the murine system, thus serving as an important signal molecule for bidirectional communication between the neuroendocrine and the immune systems.
Cell Mol Neurobiol 1995 Apr
PMID:Presence of interleukin-10 transcripts in human pituitary and hypothalamus. 859 Apr 58

Limited information is available about the pathogenesis of acquired immune deficiency syndrome (AIDS)-associated idiopathic interstitial pneumonitis, a common noninfectious complication of human immunodeficiency virus (HIV) infection. Infection of C57B1/6 mice with LP-BM5 retrovirus, a murine model of AIDS, leads to development of a diffuse interstitial pneumonitis that displays many features of human AIDS-associated interstitial pneumonitis. To further characterize the cellular and molecular features of this lung disease, the temporal development of cellular infiltration, cytokine expression, and virus replication were evaluated in lung tissue of virus-infected mice. Persistent expression of viral RNA was detectable in lungs as early as 1 wk after infection. Infiltration of the lungs by CD4+ and CD8+ T cells, by IgG+ and IgA+ B cells, and by macrophages was observed by 4 wk after infection and continued through 8 wk of infection. Histologically, cellular infiltration was most pronounced in peribronchial and perivascular regions, whereas inflammation of alveolar septae and alveolar spaces was minimal. In contrast to normals, T cells from infected lungs were immunodeficient in that they failed to proliferate in response to the mitogen concanavalin A (ConA). However, evaluation of cytokine mRNA expression by interstitial lung lymphoid cells indicated that cells from infected lungs were chronically activated, in that elevated expression of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) was observed throughout the course of infection. Similarly, expression by interstitial lung lymphoid cells of mRNA for the proinflammatory cytokine IL-1 and the fibrogenic cytokine transforming growth factor-beta (TGF-beta) was also increased following infection. These results indicate that retrovirus-induced immunodeficiency in mice is associated with infiltration and chronic activation of lymphoid cells in the lungs. Furthermore, simultaneous expression of IL-10, IFN-gamma, and TGF-beta suggests that cytokine-expressing cells in infected lungs may be unresponsive to inhibitory and antiinflammatory effects of IL-10 and/or TGF-beta, thus contributing to chronicity of inflammation in this disorder.
Am J Respir Cell Mol Biol 1997 Feb
PMID:Pulmonary lymphoid cell activation and cytokine expression in murine AIDS-associated interstitial pneumonitis. 903 22

Fifteen murine hybridoma lines that produce monoclonal antibodies against human interleukin-10 (IL-10), which is one of the most important regulatory cytokines of the immune system, were raised. Twelve of these antibodies, all in the class IgG1/kappa, recognize three groups of epitopes: A, B and C. All antibodies in these groups inhibit binding of antibodies of the same group to IL-10 and none of them inhibit binding of an antibody of another group. Two IgM/kappa antibodies and one IgG1/kappa antibody, with low affinity, have distinct binding properties and cannot be assigned to one of these groups. Antibodies from all three epitope groups inhibit the biological activity of IL-10. The three antibodies of group A neutralize IL-10 in an approximately equimolar ratio, at concentrations as low as 10 pM. In addition to their high neutralizing capacity, antibodies of group A enhance the binding of antibodies of group C to IL-10. The on-rate of binding of the two antibodies CB/RS/10 and 11 (group C) increased five- to seven-fold, when one of the antibodies CB/RS/1, 2 or 14 (group A) is bound to IL-10.
Mol Immunol 1996 Oct
PMID:Neutralizing murine monoclonal anti-interleukin-10 antibodies enhance binding of antibodies against a different epitope. 904 76

The crystal structure of Epstein-Barr virus protein BCRF1, an analog of cellular interleukin-10 (IL-10), has been determined at the resolution of 1.9 A and refined to an R-factor 0.191. The structure of this cytokine is similar to that of human IL-10 (hIL-10), forming an intercalated dimer of two 17 kDa polypeptides related by a crystallographic 2-fold symmetry axis. BCRF1 exhibits novel conformations of the N-terminal coil and of the loop between helices A and B compared to hIL-10. These regions are likely to be involved in binding of one or more components of the IL-10 receptor system, and thus the structural differences may account for the lower binding affinity and limited spectrum of biological activities of viral IL-10, compared to hIL-10.
J Mol Biol 1997 May 02
PMID:Crystal structure of Epstein-Barr virus protein BCRF1, a homolog of cellular interleukin-10. 915 83

Plasma levels of antiinflammatory compounds (which counteract inflammation, cortisol, IL-1 receptor antagonist, IL-1ra; soluble IL-2 receptor, sIL-2r, soluble intercellular adhesion molecule-1, sICAM-1; interleukin-10, IL-10) were synchronously determined in a consecutive series of 25 patients with severe bacterial infections. Serum levels of cortisol, IL-1ra, sIL-2r, sICAM-1 and IL-10 were significantly higher in patients with infection compared with healthy volunteers. Bacterial infection results in the production of inflammatory and proinflammatory cytokines from macrophage/monocyte, which are thought to be involved in the pathogenesis of systemic inflammatory response syndrome (SIRS). We found that counter-inflammatory compounds can also be released during infectious insults. These results suggested that the biological activity of inflammatory mediators is inhibited by natural antiinflammatory compounds, and the body itself might down-regulate excessive inflammatory cascades through counteracting the inflammatory responses and restore homeostasis.
Res Commun Mol Pathol Pharmacol 1997 Apr
PMID:Clinical value of cytokine antagonists in infectious complications. 917 65

We have characterized the interaction of two monoclonal antibodies with their respective antigens using cellulose-bound sets of overlapping peptides (peptide scans). Both antibodies CB/RS/5 and CB/MT/1 recognize discontinuous epitopes present in human interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-alpha). In addition, the interaction between TNF-alpha and its 55-kDa receptor (TNF-R) was investigated by the same approach. Both antibodies, as well as TNF-alpha, interacted with two or more regions of the peptide scans. Antibody-binding competition studies between the native antigens and peptides, covering single parts of the binding regions, enabled us to distinguish between binding to the paratope or other regions of the antibody. The combination of these experimental approaches allowed the identification of short antigen-derived sequences that are separated on the primary sequence but close in space on the surface of IL-10 and TNF-alpha, thus representing putative discontinuous epitopes. In the case of the TNF-R-derived peptide scans, two of the identified regions interact with the structurally similar TNF-beta in the TNF-beta-TNF-R complex. These data indicate that this approach should be generally applicable for mapping nonlinear protein-protein contact sites.
Mol Divers 1996 May
PMID:Mapping protein-protein contact sites using cellulose-bound peptide scans. 923 5

There is evidence that, following exposure to crystalline silica, the release of several proinflammatory cytokines contributes to the induction of unbalanced inflammatory reaction leading to lung fibrosis. We have examined the potential contribution of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the development of silicosis. In a mouse model of inflammatory lung reaction induced by intratracheal instillation of silica (0.5 mg and 5 mg DQ12/mouse), the levels of IL-10 protein (determined by ELISA) both in cells obtained after bronchoalveolar lavage (BAL) and in lung tissue homogenates were significantly increased when compared with controls. After in vitro lipopolysaccharide (LPS) stimulation (1 microg/ml), BAL cells obtained from silica-treated animals produced significantly more IL-10 protein and mRNA than cells obtained from control animals. To examine the role of IL-10 in the lung reaction induced by silica, IL-10-deficient animals were instilled with 5 mg of silica. Twenty-four hours after treatment, the amplitude of the inflammatory response (lactate dehydrogenase [LDH], protein and number of inflammatory cells in BAL) was significantly greater in IL-10-deficient animals than in the wild type. In contrast, the fibrotic response, evaluated by measuring lung hydroxyproline content and by histopathologic analysis 30 days after silica, was significantly less important in IL-10-deficient than in wild-type mice. Together, these data suggest that increased IL-10 synthesis induced by silica can limit the amplitude of the inflammatory reaction, but also contributes to amplify the lung fibrotic response.
Am J Respir Cell Mol Biol 1998 Jan
PMID:Role of interleukin-10 in the lung response to silica in mice. 944 45

Treatment of human peripheral blood leukocytes (hPBL) with Sendai virus induces significant production of human interferon-alpha (IFN-alpha). Addition of human recombinant interleukin-10 (IL-10) to hPBL in vitro prior to treatment with Sendai virus resulted in considerable inhibition of IFN-alpha production. Downregulation of IFN-alpha production was IL-10 concentration-dependent and observed at IL-10 concentrations of as low as 0.05 ng/ml, with a median effective dose (ED50) of about 5 ng/ml. Inhibition of IFN-alpha production by IL-10 occurred at an early stage of Sendai virus induction. The inhibitory effect of IL-10 on leukocyte interferon production was specific and blocked by pretreatment with neutralizing polyclonal anti-IL-10 antibody. This downregulatory effect is at the transcriptional level, since IL-10 inhibits IFN-alpha mRNA accumulation upon Sendai virus treatment. These data suggest that leukocyte IFN-alpha production is a highly regulated process that is modulated by cytokines such as IL-10 during early immunological response to infection.
Cytokines Cell Mol Ther 1998 Mar
PMID:Inhibitory effect of interleukin-10 on human leukocyte interferon-alpha production by Sendai virus. 955 12


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