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 interleukin-6 (IL-6) promoter is rapidly and transiently activated with other cytokines, including IL-1, tumor necrosis factor, and platelet-derived growth factor, as well as phorbol esters and agents that increase intracellular cyclic AMP. In this study, we have investigated cis-acting regulatory elements and trans-acting factors responsible for IL-1-induced IL-6 gene expression. Studies on the 5' deletion mutants of the human IL-6 gene suggested that the IL-1-responsive element was mapped within the IL-6 promoter region (-180 to -123) which was homologous to the c-fos serum-responsive enhancer element. Gel retardation assay identified two types of nuclear factors that bound to this region, one constitutive and the other inducible. These two factors recognized a 14-base-pair (bp) palindromic sequence, ACATTGCACAATCT. Furthermore, three copies of this 14-bp palindrome conferred IL-1 responsiveness to the basal enhancerless IL-6 promoter, indicating that a 14-bp-dyad symmetry sequence was an IL-1-responsive element in the IL-6 gene.
Mol Cell Biol 1990 Jun
PMID:Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1-responsive element in the IL-6 gene. 211 42

We examined expression and cytotoxic triggering capability of the three Fc receptors for IgG (Fc gamma R) on human monocytes, PMNs and myeloid cell lines after in vitro culture with various cytokines. Fc gamma R expression was evaluated using specific anti-Fc gamma R monoclonal antibodies (mAb). The cytotoxic capability of each Fc gamma R was examined after the effector cells were treated with the recombinant cytokines IFN-gamma. TNF alpha, GM-CSF, G-CSF, M-CSF, IL-1, IL-2, IL-3, IL-4, or IL-6. Hybridoma cell lines (HC) bearing antibody directed to Fc gamma RI (HC 32), Fc gamma RII (HC IV.3) or Fc gamma RIII (HC 3G8) were used as targets, as were chicken erythrocytes (CE) sensitized with heteroantibodies composed of anti-Fc gamma R mAbs (32, IV.3, 3G8) linked to anti-CE antibody. Only IFN-gamma treatment significantly increased Fc gamma R expression and then only Fc gamma RI. IFN-gamma dramatically up-regulated Fc gamma RI expression on all cells tested. However, ADCC was enhanced by treatment with a number of cytokines other than IFN-gamma. GM-CSF, TNF, and IFN-gamma treatment enhanced killing of HC 32 and HC IV.3 by in vitro cultured monocytes. G-CSF treatment enabled PMNs to kill HC through Fc gamma RII, whereas PMN killing of HC through Fc gamma RIII could not be induced by any of the cytokines studied. Although only IFN-gamma treatment increased ADCC of CE by monocytes, GM-CSF treatment as well as IFN-gamma treatment augmented ADCC of CE by PMNs. In addition to IFN-gamma treatment, IL-6 treatment enabled U937 cells to lyse CE. Whereas IFN-gamma-treated U937 cells killed CE through both Fc gamma RI and Fc gamma RII, IL-6-treated U937 cells killed CE only through Fc gamma RI. In addition to IFN-gamma treatment, G-CSF treatment enabled HL-60 cells to lyse CE through both Fc gamma RI and Fc gamma RII. These results demonstrate that although IFN-gamma appears unique in regulating Fc gamma R expression on myeloid cells, cytokines other than IFN-gamma affect ADCC by these cells in a receptor-specific manner.
Mol Immunol 1990 Jan
PMID:The effect of cytokines on the expression and function of Fc receptors for IgG on human myeloid cells. 213 46

Human interleukin 4 (IL-4) upregulates Fc epsilon R2/CD23 expression on the surface of B lymphocytes. Here it is shown that IL-4 induces expression of CD23 mRNA in normal human B lymphocytes whereas recombinant IL-1, IL-2, IL-5, IFN gamma, IFN alpha 2b and semi-purified low molecular weight B cell growth factor were unable to do so. CD23 mRNA expression could be observed in B cells after 6 hr incubation with IL-4 and was maximal for 24-72 hr. Costimulation of the B cells with anti-IgM antibody enhanced the IL-4 induced CD23 mRNA expression. In contrast, IFN gamma and IFN alpha 2b inhibited IL-4 induced CD23 mRNA expression in normal B lymphocytes. Thus the regulatory effects of IL-4 and interferons on the CD23 membrane expression are linked to an increase and a decrease of CD23 transcripts respectively.
Mol Immunol 1990 Feb
PMID:Interleukin 4 and interferons alpha and gamma regulate Fc epsilon R2/CD23 mRNA expression on normal human B cells. 213 8

The effect of interleukin (IL)-6 and IL-1 on the biosynthesis of complement components C3, factor B, C2, C4 and C1 inhibitor (C1 inh), as well as that of albumin, was studied in vitro in human hepatoma-derived cell line, HepG2. Measuring the amounts of secreted complement proteins we detected a significant upregulation of C3 by both hormones. The enhancement of the factor B and especially that of C1 inh production was predominant by IL-6. In our experimental system neither IL-1 nor IL-6 affected the biosynthesis of C2 and C4. Albumin secretion was significantly decreased only in the simultaneous presence of IL-1 and IL-6. Detection of the changes in the amounts of C3- and factor B-specific mRNA of HepG2 cells suggests a pretranslational regulation by these cytokines. The secretion of C3 and factor B was markedly potentiated when IL-1 and IL-6 were added together. However only the gene expression of factor B, but not of C3, was found to reveal synergism. IL-6 enhanced the in vitro production of C3 in mouse hepatocytes as well. This effect was greatly potentiated in the presence of histamine.
Mol Immunol 1990 Feb
PMID:Hormonal regulation of complement biosynthesis in human cell lines--II. Upregulation of the biosynthesis of complement components C3, factor B and C1 inhibitor by interleukin-6 and interleukin-1 in human hepatoma cell line. 215 45

We investigated the effects of silica (SiO2) and titanium dioxide (TiO2) on the pulmonary recruitment of inflammatory cells and the ability of alveolar macrophages (AMs) to release the pro-inflammatory cytokines, interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF). Rats were intratracheally instilled with 5 to 100 mg/kg of the materials, and bronchoalveolar lavage cell populations and AM cytokine release were characterized on days 1, 7, 14, and 28. Both dusts elicited dose-related increases in neutrophils, lymphocytes, and AMs; however, this response was more pronounced and persistent with SiO2. SiO2 at greater than or equal to 50 mg/kg increased AM release of IL-1 and TNF at all time points; lower SiO2 doses had either a transient or no effect on AM-derived cytokines. TiO2 did not result in AM IL-1 release and increased TNF release transiently at doses greater than or equal to 50 mg/kg. Both dusts primed AMs to release increased levels of IL-1 and TNF upon in vitro stimulation with lipopolysaccharide. Histopathology (day 28) demonstrated dose-related interstitial inflammation associated with SiO2 exposure, an effect that was less severe with TiO2. SiO2 doses of greater than or equal to 50 mg/kg elicited a granulomatous response. Development of granulomatous inflammation only at SiO2 doses for which persistent AM IL-1 release occurred suggests involvement of this cytokine in the formation of SiO2-induced granulomas. The ability of SiO2 to activate AM release of IL-1 and TNF in a more pronounced and persistent manner than TiO2 is likely responsible, at least in part, for the greater inflammation and pneumotoxicity associated with SiO2.
Am J Respir Cell Mol Biol 1990 Apr
PMID:Pulmonary response to silica or titanium dioxide: inflammatory cells, alveolar macrophage-derived cytokines, and histopathology. 215 74

Interleukin-6 (IL-6) modulates a number of processes relevant to host immunity and inflammation. We investigated the capacity of the human alveolar macrophage to elaborate IL-6 in response to lipopolysaccharide (LPS), recombinant interleukin-1 (rIL-1), and recombinant tumor necrosis factor (rTNF), and compared macrophage IL-6 production to that of blood monocytes and lung fibroblasts. Unstimulated and TNF-stimulated alveolar macrophages and monocytes produced little or no detectable IL-6. In contrast, macrophages and monocytes produced large amounts of IL-6 in response to LPS and monocytes produced lesser but readily detectable amounts in response to rIL-1. Monocytes and alveolar macrophages differed significantly in their capacity to produce IL-6, with macrophages making more IL-6 in response to LPS and less IL-6 in response to rIL-1 than autologous blood monocytes. Monocytes aged in vitro produced little detectable IL-6 in response to LPS or rIL-1, suggesting that differences in cell maturity may account for the diminished capacity of the alveolar macrophage to produce IL-6 in response to IL-1 but not its enhanced capacity to produce IL-6 in response to LPS. Mononuclear phagocytes and lung fibroblasts also differed in their ability to produce IL-6. Lung fibroblasts produced more IL-6 in response to rIL-1 and less IL-6 in response to LPS than monocytes and macrophages. In addition, monocytes and macrophages elaborated electrophoretically identical IL-6 moieties that differed from those produced by lung fibroblasts. These differences could be at least partially attributed to differences in sialylation and/or glycosylation.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1990 Nov
PMID:Human alveolar macrophage and blood monocyte interleukin-6 production. 222 4

The growth of adherent synovial cells passaged once was studied in response to human recombinant interleukin 1 (hr IL-1) beta. Human synovial cell cultures were established from tissues obtained during therapeutic joint surgery for patients with rheumatoid arthritis (rheumatoid synovial cells, RSC) or non inflammatory rheumatic diseases (non rheumatoid synovial cells, NRSC). The effect of IL-1 beta (0.1 to 10 ng/ml) on the time course of proliferation showed that values for DNA synthesis and cell numbers in RSC cultures were higher than in NRSC cultures. Similarly, untreated control RSC cultures grew more quickly than NRSC. These results demonstrate that RSC, which are continuously stimulated by IL-1 beta produced in the rheumatoid pannus in vivo, have a higher capacity for proliferation than NRSC but are less responsive to IL-1 beta. A dose-response curve of proliferation was established 72 hrs. after the addition of IL-1 to the medium. The stimulating effect of IL-1 beta (0.001 to 10 ng/ml) was dose-dependent in both RSC and NRSC and reached a plateau at 10 ng/ml; the response of NRSC was stronger than that of RCS.
Cell Mol Biol 1990
PMID:Effects of human recombinant IL-1 beta on rheumatoid and non rheumatoid human synovial cell growth. 222 55

The pathophysiology of bone loss in castrated animals is reviewed. Both male and female rats rapidly lose metaphyseal trabecular bone from the tibia and the femur due to an imbalance between bone resorption and bone formation. The aetiology of sex hormone deficiency-induced bone loss is not fully understood. It seems unlikely that the bone loss is due to changes in the circulating levels of the calciotropic hormones or to an increase in the spontaneous release from peripheral blood monocytes of the bone resorption stimulating cytokine IL-1. Changes in the sensitivity of bone of castrated rats to calciotropic hormones may play a role as well as the lack of direct stimulatory effects of gonadal oestrogens and androgens on bone cells. In addition several data indicate that prostaglandins may be involved.
J Steroid Biochem Mol Biol 1990 Nov 20
PMID:Pathophysiology of bone loss in castrated animals. 225 51

The adhesion of leukocytes to endothelium is a physiological phenomenon which is the first step for leukocyte emigration. The adhesion can be dramatically increased in pathological situations such as inflammation and vascular diseases. The molecular basis of leukocyte-endothelium interaction has been largely investigated in the last ten years. Using monoclonal antibodies it is possible to characterize the leukocyte adhesion molecule (LeuCAM) also named CD11/CD18 complex. These molecules responsible for leukocyte adhesion are heterodimers consisting of a common beta subunit and different subunit CD11a/CD18 corresponding to LFA-1; CD11b/CD18 to Mac1/Mol; CD11c/CD18 to GP150-95. Beside these receptors, other leukocyte structures such as the fibronectin receptors are involved in the adhesive process. On the endothelial cell side specialized structures implicated in leukocyte adhesion have been identified. Structures like Intercellular Adhesion Molecule (ICAM) are expressed on endothelial cells in the absence of stimulation, while other receptors Endothelial Leukocyte Adhesion Molecule (ELAM) are only detectable on activated endothelial cells. Cytokines such as IL-1 induced the expression of ELAM, increased the number of ICAM and Human Leukocyte Antigens (HLA) DR, DP, DQ. In various pathological circumstances, namely extracorporeal circulation, Acute Respiratory Distress Syndrome (ARDS), hypercholesterolemia and diabetes mellitus increased leukocyte adhesion has been reported and is potentially responsible for vascular damage. Therefore, the modulation of leukocyte-endothelial cell interactions is a possible target for antithrombotic and antiatherosclerotic therapy.
 ...
PMID:Leukocyte adhesion to endothelial cells. 226 8

After administration of the cytokines interleukin 1 (IL1), tumor necrosis factor (TNF), interleukin 2 and interleukin 6 to laboratory animals or humans, plasma levels of glucocorticoids are elevated. This effect is mediated by activation of the hypothalamic-pituitary unit. IL1 and TNF inhibit aldosterone production by rat adrenocortical cells in vitro and stimulate renin release by rat renal cortical cells. Administration of IL1 or TNF in rats suppresses hypothalamic-pituitary-thyroid function, whereas IL1 acts at the level of the brain and the gonads to interfere with gonadotropin and sex steroid secretion. During stimulation of the immune system (e.g. during infectious diseases), peculiar alterations in hormone secretion occur (hypercortisolism, hyperreninemic hypoaldosteronism, euthyroid sick syndrome, hypogonadism). The role of cytokines in these alterations remains to be established.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Cytokines and the hypothalamic-pituitary-adrenal axis. 228 99


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