Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the proliferation of lymphocytes and on the production of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) was examined in normal human peripheral blood mononuclear cells (PBMC) activated in vitro either by phytohaemagglutinin (PHA) or by the monoclonal antibody to the T-cell receptor OKT3, or by the combination of each of these two stimuli with phorbol myristate acetate (PMA). 1,25(OH)2D3 inhibited the proliferative response of PBMC to PHA; this effect, however, was abrogated by the addition of PMA (1.6 nM), and it was reversed from inhibition to stimulation by higher concentrations of the phorbol ester. In contrast to the PHA-activated cells, 1,25(OH)2D3 had no effect on the proliferative response of PBMC to OKT3. Further, 1,25(OH)2D3 inhibited the release of IL-6 in cultures of PHA-activated PBMC, whereas it stimulated IL-6 with the addition of PMA in these cultures. In contrast to the PHA-activated cells, 1,25(OH)2D3 increased IL-6 release in OKT3-activated cells. IL-1 beta production was not affected in either PHA- or OKT3-activated cells by the presence of the hormone, but it was stimulated by 1,25(OH)2D3 when PMA was used as a co-stimulus with either PHA or OKT3. Finally, 1,25(OH)2D3 inhibited IFN-gamma in both PHA- and OKT3-activated cells, but these effects were attenuated in the presence of PMA. These findings demonstrate that the in vitro effects of 1,25(OH)2D3 on lymphocyte proliferation and cytokine production by PBMC are pleiotropic, and that such pleiotropism depends upon the mode of PBMC activation and presumably the signals that are generated in response to the specific agents used to activate these cells.
Immunology 1992 Dec
PMID:Signal-dependent pleiotropic regulation of lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3: potent modulation of the hormonal effects by phorbol esters. 149 24

Ethanol alters many metabolic processes within the liver. Both ethanol abuse and the inability to mount an acute phase response (APR) have been associated with an increased morbidity and mortality in critically ill patients. To determine if ethanol influences the hepatic APR, relative amounts of two different human acute phase protein mRNA's were examined in the human hepatoma cell line Hep 3B before and after exposure to ethanol. Hep 3B cells were treated with one or more of the following: ethanol ((E) 150 mM); interleukin-1 beta ((IL-1) 200 units/ml); or interleukin-6 ((IL-6) 50 units/ml). After a 12-20 hr incubation relative amounts of mRNA for a1-protease inhibitor (PI) or beta fibrinogen were determined by Northern blot hybridization. Both ethanol and IL-6 were found to induce a1-PI mRNA. Fibrinogen mRNA was induced by IL-6 but not by ethanol, and no induction of PI or fibrinogen mRNA was found with IL-1. This suggests that under certain conditions, ethanol may influence acute phase protein metabolism. To our knowledge, this is the first description of an ethanol induced alteration of acute phase protein mRNA.
J Surg Res 1991 Dec
PMID:Ethanol induces a1-protease inhibitor mRNA in Hep 3B cells. 165 92

Communication circuits operating between activated monocytes/macrophages and adjacent hepatocytes in the liver effect important alterations in hepatocyte function. We demonstrate here that primary human hepatocytes and hepatoma cells are able to function as effector cells in the recruitment of inflammatory cells in hepatic disease and inflammatory states by synthesizing a neutrophil/lymphocyte chemotactic factor, interleukin-8. We have further investigated the possibility that endogenous factors elaborated by activated peripheral blood monocytes and Kupffer cells in the liver are mediators of hepatocyte-derived interleukin-8 expression. Twenty-four-hour conditioned medium from lipopolysaccharide-stimulated peripheral blood monocytes and nonparenchymal human liver cells enriched for Kupffer cells induced a time-dependent increase in interleukin-8 messenger RNA levels in SK-hepatoma cells over a 24-hr period, similar to that seen for tumor necrosis factor-alpha or interleukin-1 beta induction of interleukin-8 in primary hepatocytes. Exogenously added lipopolysaccharide or recombinant interleukin-6 had no effect. Cell-associated interleukin-8 antigen was present in SK-hepatoma and primary hepatocytes that had been incubated with macrophage-conditioned medium, tumor necrosis factor or interleukin-1 beta. Similarly, neutrophil chemotactic activity was secreted by SK-hepatoma cells, a significant proportion of which could be blocked with interleukin-8--specific antiserum. Preincubation of macrophage-conditioned medium with neutralizing antibodies to tumor necrosis factor-alpha or interleukin-1 beta reduced its interleukin-8 messenger RNA-inducing capacity. Exposure of SK-hepatoma to conditioned medium followed by removal of the stimulus resulted in a rapid down-regulation of interleukin-8 messenger RNA to 50% of the maximum level within the first hour. These data suggest that products derived from activated Kupffer cells can modulate hepatoma cells and primary hepatocyte interleukin-8 gene expression. In addition, macrophage/monocyte-derived tumor necrosis factor-alpha and interleukin-1 beta have major roles in the positive regulatory component of this modulation.
Hepatology 1991 Dec
PMID:Kupffer cell-derived cytokines induce the synthesis of a leukocyte chemotactic peptide, interleukin-8, in human hepatoma and primary hepatocyte cultures. 166 18

The nature of the events that precipitate autoimmune diseases varies. Interleukin-1 and tumor necrosis factor do not precipitate autoimmune diseases but rather act as effector molecules. They induce eicosanoid and nitric oxide synthesis, stimulate collagenases and collagen synthesis, and trigger the genes for other cytokines, namely interleukin-2, interleukin-6 and interleukin-8. The ability to block interleukin-1 with the receptor antagonist, and tumor necrosis factor with soluble receptors, has given investigators specific tools to test the role of these two cytokines in the pathological processes of autoimmune disease.
Curr Opin Immunol 1991 Dec
PMID:Inflammatory cytokines: interleukin-1 and tumor necrosis factor as effector molecules in autoimmune diseases. 166 33

Mucosal exposure to Escherichia coli elicits an inflammatory response in the urinary tract. Interleukin-6 (IL-6) is secreted into the urine, and polymorphonuclear leukocytes (PMNLs) are recruited to the site of infection. This study analyzed the ability of mucosally administered bacterial components to activate IL-6 and PMNL responses. P, S, and type 1 fimbrial preparations with adhesins specific for Gal alpha 1-4Gal beta, NeuAc alpha 2-3Gal, and mannose, respectively, were inoculated intravesically into lipopolysaccharide (LPS)-responder (C3H/HeN) and LPS-nonresponder (C3H/HeJ) mice. The role of the fimbrial adhesin was examined by comparing P and S fimbriae with (Adh+) and without (Adh-) the receptor-binding domain. Isolated lipid A was used in parallel. The urinary IL-6 levels were elevated after challenge with Adh+ P fimbriae, but not after challenge with the Adh- P fimbriae, Adh+ or Adh- S fimbriae, or type 1 fimbriae. The activation was not a function of contaminating LPS, since it occurred in both LPS-responder and -nonresponder mice and since isolated lipid A was a poor activator of the IL-6 response. In contrast, lipid A was a potent inducer of the PMNL response. The results suggested that the IL-6 and PMNL responses were activated via different pathways; the IL-6 response was activated mainly by an adhesion-dependent interaction with the mucosa, and the PMNLs were activated mainly by lipid A. The results emphasize the active role of the mucosal barrier in the production of mediators in response to diverse bacterial stimulants.
Infect Immun 1991 Dec
PMID:Adhesion-dependent activation of mucosal interleukin-6 production. 168 60

Some myeloma cells freshly isolated from bone marrow aspirates in human myelomas and some myeloma cell lines formed spontaneous cell aggregations in vitro (homotypic cell aggregations). In order to clarify the surface molecules involved in homotypic cell aggregations and physiological roles of these cell aggregations, we investigated the expressions of intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 1 (LFA-1) on 20 samples of freshly isolated myeloma cells and three myeloma cell lines and the effect of anti-ICAM-1 and anti-LFA-1 alpha antibodies on myeloma cell proliferation in vitro. All myeloma cells that we tested expressed ICAM-1 on their surface. Among them, myeloma cells that strongly coexpressed LFA-1 alpha, formed homotypic cell aggregates in vitro. These spontaneous cell aggregations were completely released by adding either anti-ICAM-1 or anti-LFA-1 alpha antibody. During short-term culture, spontaneous proliferation of myeloma cells in vitro and their proliferative responses to recombinant interleukin-6 (rIL-6) were not affected by pretreatment of myeloma cells with anti-ICAM-1 or anti-LFA-1 alpha antibody. Therefore these data suggest that homotypic cell aggregation of myeloma cells is mediated by ICAM-1 and LFA-1 molecules, but myeloma cell proliferation may not be modulated by these adhesion molecules during short-term cultures.
Br J Haematol 1991 Dec
PMID:Homotypic cell aggregations of human myeloma cells with ICAM-1 and LFA-1 molecules. 168 27

Incubation of alpha 1-antichymotrypsin-cathepsin G complexes with human lung fibroblasts caused a nearly 5-fold increase in synthesis of the cytokine interleukin-6. In turn, the fibroblast-conditioned medium induced significant synthesis of the acute phase proteins haptoglobin, fibrinogen, and alpha 1-antichymotrypsin in human Hep G2 cells, whereas a mixture of interleukin-1 and conditioned medium was considerably less stimulatory. These data indicate that proteinase-proteinase inhibitor complexes formed between plasma serpins and their target enzymes could play major roles in signaling for acute phase protein synthesis in response to injury.
J Biol Chem 1990 Dec 05
PMID:Acute phase protein stimulation by alpha 1-antichymotrypsin-cathepsin G complexes. Evidence for the involvement of interleukin-6. 170 Nov 74

Cells of the macrophage lineage are considered to be of special importance in the defense of the host against tumor development and spread. Immunotherapeutic strategies to stimulate macrophage (MAC) tumor cytotoxicity make use of activating compounds such as gamma-interferon which are given systemically. However, there are several lines of evidence that in malignant disease the generation of cytotoxic effector MACs is impaired. Both defective cell maturation and loss of responsiveness to activation are described. Here, a first clinical phase I trial of adoptive immunotherapy in cancer patients using autologous MACs generated in vitro from blood monocytes (MOs) is reported. Mononuclear cells were isolated by cytapheresis and density centrifugation and cultured in hydrophobic Teflon bags for 7 days with 2% autologous serum and recombinant human gamma-interferon being present for the last 18 h. Cytotoxic MO-derived MACs were then purified by countercurrent elutriation and reinfused into the patient. A total of 72 therapies have been performed with patients being treated i.v. (n = 8) and i.p. (n = 7). In vitro generated MACs proved to be mature as judged by the expression of maturation-associated surface molecules (MAX antigens, CD16, CD51, CD71), were cytotoxic to U937 tumor cells, and were efficient secretory cells. Cell dose escalation was performed in the first patients beginning with 10(8) MACs to finally infuse the total number of cells recovered from one single cycle of isolation and culture. MAC yield varied from 1 to 17 x 10(8) representing 13-79% of MOs initially seeded. Adoptive MAc transfer was well tolerated. Side effects observed were low-grade fever (less than 38.5 degrees C), induction of the coagulation cascade, and abdominal discomfort after i.p. application. The procoagulant activity of MAC autografts was cell dose dependent and demonstrated by detection of circulating fibrin monomers and thrombin-antithrombin complexes. Biological responses observed included elevated serum neopterin levels and the appearance of interleukin-6 in sera and ascitic fluids. Indication of a possible therapeutic effect was only observed in i.p.-treated patients and consisted of disappearance of malignant ascites in 2 of 7 patients.
Cancer Res 1990 Dec 01
PMID:Adoptive transfer of tumor cytotoxic macrophages generated in vitro from circulating blood monocytes: a new approach to cancer immunotherapy. 170 43

The production of interleukin (IL) 6 from six human liver cell lines, including Chang liver, HLF, HLE, HepG2, PLC/PRF/5, and HuH-7, was investigated using enzyme-linked immunosorbent assay and Northern blot analysis. When cells were cultured in the presence of 12-O-tetradecanoylphorbol-13-acetate, significant amounts of IL6 were detected in the culture supernatants of Chang liver cells, HLF cells, and HLE cells. However, IL6 was not detected in the culture supernatants from HepG2 cells, PLC/PRF/5 cells, or HuH-7 cells which had been treated similarly. To further investigate the production of IL6, expression of the IL6 gene was studied. Results of Northern blot analysis using IL6 complementary DNA as a probe showed that the induction was initiated at the mRNA level. Moreover, IL6 mRNA was also induced by IL1 beta and tumor necrosis factor but not by a calcium ionophore (A23187) or IL6 itself in Chang liver cells. This is the first study to demonstrate the production of human IL6 in liver cells. Furthermore, when the production of alpha-fetoprotein (AFP) from the liver cell lines was examined, the three that were able to produce IL6 failed to produce AFP, whereas the other three cell lines succeeded in producing AFP. These observations may indicate the heterogeneous origin of the liver cell lines.
Cancer Res 1990 Dec 01
PMID:Production of interleukin 6 from human liver cell lines: production of interleukin 6 is not concurrent with the production of alpha-fetoprotein. 170 44

The skin as an organ contains a large pool of cells, important for the production of various cytokines. This study focuses on interferon-beta (IFN-beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) production by fibroblasts and epithelial cells in response to interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). Both these primary cytokines show multiple biologic activities in the skin. Their antiviral activity on fibroblasts is mediated by IFN-beta and not by IL-6. In addition, TNF-alpha and IL-1 have a growth stimulatory effect on dermal fibroblasts, which is not mediated by IFN-beta or IL-6. IL-1, double-stranded RNA, or virus are potent inducers of IL-6 and IL-8 on dermal fibroblasts, but they are less efficient on epidermal cells. IL-8 has been discovered as an early acting skin reactive factor responsible for the chemotaxis of neutrophilic granulocytes. Furthermore, IL-1 possesses delayed skin reactivity upon intradermal injection which presumably is mediated by local release of IL-8. These findings demonstrate that cytokines also interact in the skin and that dermal fibroblasts play an important role in the regulation of aspecific host defense.
J Invest Dermatol 1990 Dec
PMID:Interaction of interferons with skin reactive cytokines: from interleukin-1 to interleukin-8. 170 15


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