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)

Monocyte chemoattractant protein 1 (MCP-1) is a member of the chemokine superfamily of genes that induces chemotaxis of monocytes in inflammatory processes. The effects of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF-BB), parathyroid hormone (PTH), and 1,25(OH)2D3 on MCP-1 expression in human osteoblastic cells were compared. Inflammatory or proinflammatory cytokines stimulated the production of MCP-1 in normal human osteoblastic cells as determined by RIA. The osteotrophic mediators PTH and 1,25(OH)2D3 and PDGF-BB had no effect on MCP-1 expression. In further studies, the steady-state mRNA and MCP-1 protein levels in two human osteoblastic cell lines, MG-63 and SaOS-2, were examined. MCP-1 expression at both the protein and mRNA levels was greatly increased by IL-1 beta and TNF-alpha. At the mRNA level, IL-1 beta and TNF-alpha strongly induced MCP-1 expression; TGF-beta and IL-6 induced MCP-1 but to a lesser extent. No significant changes in MCP-1 mRNA or MCP-1 protein secretion were observed when cells were treated with PDGF-BB, PTH, and 1,25(OH)2D3. When tested on preosteoclasts, MCP-1 was shown to have no effect on the formation of multinucleated, tartrate-resistant acid phosphatase (TRAP)-positive osteoclastic cells.
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PMID:Expression of monocyte chemoattractant protein 1 in human osteoblastic cells stimulated by proinflammatory mediators. 794 60

Recent analysis of a various kinds of cytokines revealed that the cytokines are actively involved in a number of important biological functions including immunological and endocrine functions. The present study investigated the unique cytokine-mediated immunological and endocrinological functions in the intra-uterine space during pregnancy. A human placenta which expresses paternal and maternal antigens was revealed to escape from maternal immune systems by releasing immunosuppressive cytokines derived from the placenta. Placental cytokines such as interleukin-6 (IL-6) activated IL-6-receptor-mediated signal transduction pathways to produce human chorionic gonadotropin (hCG). IL-1 and tumor necrosis factor-alpha (TNF-alpha) synergistically augmented IL-6 production to stimulate hCG production. However, transforming growth factor-beta (TGF-beta) suppressed these cytokine-mediated hCG production as well as IL-6 production. Thus, these placental cytokines, mainly derived from trophoblasts, cooperatively contributed to hCG production. IL-8 and monocyte chemotactic and activating factor (MCAF) activate host defense mechanism by activating neutrophils and monocytes as well as macrophages, respectively. IL-6 also activates immune responses and promote synthesis of acute-phase reactant proteins, contributing to augmentation of host defense mechanism in a different way from IL-8 and MCAF. Human placenta in the 3rd trimester actively produced these cytokines for potentiation of placental defense mechanism during pregnancy and in chorioamnionitis. A fetus in chorioamnionitis also produced these cytokines in utero for potentiation of fetal defense mechanism. Among these cytokines, IL-8 in a cord serum was a very sensitive and useful marker for clinical diagnosis of chorioamnionitis. Cord serum IL-6, in contrast, stimulated the synthesis of surfactant protein-A (SP-A) to promote fetal lung maturation and reduce the incidence of RDS. Collectively, the present study revealed the cytokine network in the placenta regulating maternal immune responses, placental endocrine functions, feto-maternal defense mechanism and fetal respiratory maturation.
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PMID:[Immunological analysis of the mechanism of maternal tolerance of a fetus and the cytokine-mediated regulation of feto-placental functions]. 808 6

Macrophage-like synoviocytes originate in the bone marrow, like other mononuclear phagocytes, and are constantly replaced via the circulation. In rheumatoid synovium sections, 80-100% of the synovial lining cells are macrophage-like cells functioning as antigen processing- and antigen-presenting cells to T lymphocytes. Monocyte and lymphocyte traffic into the rheumatoid arthritis (RA) synovium is mediated by adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecules-1 and -2 (ICAM-1 and ICAM-2), as well as monocyte chemotactic protein 1 (MCP-1) and beta 2 integrins (CD11 a,b,c/CD18). Macrophage-like cells in the RA synovium are highly activated based on their morphology, surface class II HLA antigen expression, and synthesis of cytokines such as interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage CSF, and transforming growth-factor beta (TGF-beta). Evidence for type 1 (higher affinity) and type 2 (lower affinity) androgen (ARs) and estrogen receptors (ERs) on macrophage-like synoviocytes in either male or female synovial samples from both RA patients and controls has been reported. In particular, ERs have also been found on CD8+CD29+ CD45R0+ T lymphocytes (memory), infiltrating rheumatoid synovial tissues. Sex hormones have been found to influence macrophage activity in experimental and clinical conditions such as RA. Generally estrogens have immunostimulatory effects, whereas androgens are immuno-suppressive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Macrophages, synovial tissue and rheumatoid arthritis. 839 94

The strong resemblance between the clinical manifestations of hemolytic transfusion reactions and sepsis, in which cytokine production has a central role, suggests that similar pathophysiologic mechanisms are involved. There is an expanding body of clinical and experimental evidence that cytokines, especially interleukin-1, tumor necrosis factor, interleukin-6, and interleukin-8, are principle mediators of immune responses to erythrocyte incompatibility. Recent studies have further suggested that the monocyte chemotactic and activating factor, monocyte chemoattractant protein-1, and the anti-inflammatory cytokine interleukin-1 receptor antagonist are produced in experimental models of hemolytic transfusion reactions. Differing levels and patterns of expression of these cytokines may be seen in models of intravascular hemolysis due to ABO incompatibility and extravascular hemolysis due to Rh incompatibility, which correlate with the recognized clinical differences between these two types of reactions. Furthermore, recent studies have demonstrated that several of these same cytokines are produced during the storage of platelet concentrates, which may account for some febrile reactions that are not prevented by the use of leukocyte reduction filters.
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PMID:Cytokines and erythrocyte incompatibility. 937 22

Induction of chemokine gene expression from peripheral blood mononuclear cells (PBMCs) stimulated by proinflammatory cytokines plays an important role in both wound repair and response to infectious agents. In the present study, we show that the proinflammatory cytokine interleukin-6 (IL-6) potently induced mRNA expression and secretion of the CC chemokine monocyte chemotactic protein 1 (MCP-1) in PBMCs. In addition, because human immunodeficiency virus (HIV) infection in vivo and in vitro has been shown to dysregulate the production of and/or the response to cytokines, PBMCs from both healthy uninfected and HIV-infected individuals were studied for their constitutive and IL-6-induced expression of MCP-1. No substantial differences were observed between the two groups of individuals. In addition, IL-6 upregulated MCP-1 expression in the promonocytic cell line U937 and in its chronically HIV-infected counterpart, U1. In these cell lines, IL-6 selectively induced MCP-1 and not other chemokines, including regulated upon activation normal T cells expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and IL-8. IL-6 induction of MCP-1 was partially inhibited by hydrocortisone in U1 cells. Thus, IL-6 activates PBMCs to secrete MCP-1, a CC chemokine pivotal for monocyte recruitment in tissue and organs in which important inflammatory events occur.
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PMID:Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937 cell line. 941 93

The tear film plays an important role in the defense of the external ocular surface. During sleep a number of changes take place, including increased production and release of various inflammatory mediators. We have studied the hypothesis that closed-eye tears contain proinflammatory cytokines and lipid inflammatory mediators, which serve to recruit polymorphonuclear leukocytes (PMNs) and regulate the function of PMNs and IgA during sleep. We investigated interleukin-1beta, interleukin-6, interleukin-8, monocyte chemotactic protein 1, granulocyte-macrophage colony stimulating factor (GM-CSF), leukotriene B4 (LTB4), and platelet activating factor (PAF) in open and closed-eye tears of normal healthy subjects. Results showed that IL-6, IL-8, GM-CSF, LTB4, and PAF were present in high levels in closed-eye tears compared to open-eye tears. Closed-eye tears were able to recruit neutrophils, with maximal recruitment after 8 hr of sleep, suggesting that chemokine IL-8 and the lipid chemoattractant LTB4 were active. Flow cytometric analysis revealed that incubation of neutrophils with closed-eye tears up-regulated the surface expression of IgA receptor, indicating that the GM-CSF in tears was functionally active. Up-regulation of cytokines and the lipid inflammatory mediator LTB4 during eye closure are noteworthy, as each of these cytokines has an established role in initiation and amplification of the inflammatory response. IL-8 and LTB4 may act as potent chemoattractants and activators for PMNs, whereas IL-6 and GM-CSF potentiate the secretion and function of IgA and enhance neutrophil responsiveness to proinflammatory agonists.
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PMID:The proinflammatory cytokines and arachidonic acid metabolites in human overnight tears: homeostatic mechanisms. 947 55

Interleukin-6 (IL-6) and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1) play pivotal roles in systemic inflammation, immune response, and tissue damage after cardiopulmonary bypass (CPB). Previous reports have described transient rises in IL-6 and MCAF after CPB, but the data seem to vary according to the different surgical procedures used. To evaluate the influence of the different surgical procedures on the proinflammatory cytokine responses, we compared perioperative serum IL-6 and MCAF release in coronary artery bypass grafting (CABG) and valvular surgery cases. Eighteen CABG (CABG group) and 7 single valvular cardiac surgery patients (valve group) were included in this study. Blood samples were taken to measure the serum concentrations of IL-6 at the induction of anesthesia, at the removal of the aortic cross-clamp, at the end of CPB, at the end of surgery, and 24 h after the termination of surgery. Serum IL-6 and MCAF were assayed by ELISA. Serum IL-6 increased immediately after aortic declamping and reached its peak at the end of surgery in both groups. Serum IL-6 concentrations at the end of surgery and 24 h after surgery were significantly higher in the valve group than in the CABG group (123.9 +/- 21.7 pg/ml vs. 79.7 +/- 10.4 pg/ml, p = 0.049; 113.6 +/- 25.0 pg/ml vs. 39.9 +/- 11.5 pg/ml, p = 0.006, respectively). Serum MCAF increased immediately after aortic declamping, and the MCAF level at the end of surgery was significantly higher in the valve group than in the CABG group (1118.4 +/- 353.9 pg/ml vs. 241.0 +/- 71.2 pg/ml, p = 0.002, respectively). IL-6 and MCAF may play important roles in the pathophysiology of surgical damage with CPB, and the different surgical procedures appear to affect the proinflammatory cytokine release after cardiac surgery differently.
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PMID:Influence of surgical procedures on interleukin-6 and monocyte chemotactic and activating factor responses: CABG vs. valvular surgery. 1067 Jun 46

The neurotropism of Japanese encephalitis virus (EV) has not been well characterized. Astrocytes are parts of the blood-brain barrier, a major source of chemokines, and critical effectors of central inflammation. Thus, astrocytes might play some role as JEV travels from the peripheral to the CNS and/or the resultant encephalitis. Using rat cortical cultures, we found that JEV can cause cellular and/or functional changes in astrocytes as indicated by increased expression of interleukin-6 (IL-6), regulated by activation, normal T cell expressed and secreted (RANTES), and monocyte chemotactic protein 1 (MCP-1), increased lactate release and glucose uptake, and attenuation of glutamate toxicity. These modulations occur needed by the cells for compensation and may affect neuron and/or astrocyte function.
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PMID:Astrocytic alteration induced by Japanese encephalitis virus infection. 1088 46

Experimental infection of inbred mouse strains with Candida albicans provides a good model system to identify host genetic determinants that regulate onset of, response to, and ultimate outcome of disseminated candidiasis. The A/J mouse strain is exquisitely sensitive to infection with C. albicans, while the C57BL/6J strain is relatively resistant, as measured by survival following intravenous injection of Candida blastospores. This differential susceptibility is caused by an A/J-specific loss-of-function mutation in the C5 component of the complement pathway. C5 plays several critical roles in host response to infection, including target lysis and phagocyte recruitment. Therefore, to determine which of its functions were required for host resistance to candidiasis, a detailed comparative analysis of pathophysiology and host response to acute C. albicans infection was conducted in A/J and C57BL/6J mice. C5-sufficient C57BL/6J mice were found to succumb late in infection due to severe kidney pathology, typified by fungal replication and robust neutrophil-based inflammatory response associated with extensive tissue damage. In contrast, A/J mice were moribund within 24 h postinfection but displayed little if any kidney damage despite an inability to mobilize granulocytes and a high fungal load in the kidney. Rather, C5 deficiency in A/J mice was associated with higher levels of circulating cytokines tumor necrosis factor alpha, interleukin-6, monocyte chemotactic protein 1 (MCP-1), MCP-5, and eotaxin in response to C. albicans. Transfer of the C5-defective allele from A/J onto a C57BL/6J genetic background in recombinant congenic strain BcA17 recapitulated the phenotypic aspects of the susceptibility of A/J mice to C. albicans, confirming the causative role of C5 deficiency in the dysregulated cytokine response.
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PMID:Dysregulated inflammatory response to Candida albicans in a C5-deficient mouse strain. 1538 88

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. We evaluated the efficacy of LBM415, a novel peptide deformylase inhibitor antimicrobial agent, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were intranasally inoculated once with 10(7) CFU of M. pneumoniae. Groups of mice were treated with LBM415 (50 mg/kg of body weight) or placebo subcutaneously daily for 13 days, starting 24 h after inoculation. Groups of mice were evaluated at the baseline; at days of treatment 1, 3, 6, and 13; and at 7 days after treatment. The MIC of LBM415 against M. pneumoniae was <0.005 microg/ml. LBM415-treated mice had significantly lower bronchoalveolar lavage fluid M. pneumoniae concentrations than placebo-treated mice on days 6 and 13 of treatment. Compared with placebo treatment, therapy with LBM415 significantly decreased lung histopathology scores at days 3, 6, and 13 of treatment and at 7 days after treatment. Airway obstruction was significantly lower in LBM415-treated mice than in placebo-treated mice on days 1, 3, and 6 of treatment and after 7 days of therapy, while airway hyperresponsiveness was significantly lower only on day 3 of therapy. The bronchoalveolar lavage fluid concentrations of tumor necrosis factor alpha, gamma interferon (IFN-gamma), interleukin-6 (IL-6), IL-12, KC (functional IL-8), monocyte chemotactic protein 1, macrophage inflammatory protein 1alpha, monokine induced by IFN-gamma, and IFN-inducible protein 10 were significantly reduced in LBM415-treated mice compared with the levels in placebo-treated mice. There were no differences in the bronchoalveolar lavage fluid concentrations of granulocyte-macrophage colony-stimulating factor, IL-1beta, IL-2, IL-4, IL-5, and IL-10 between the two groups of mice. LBM415 therapy had beneficial microbiologic, histologic, respiratory, and immunologic effects on acute murine M. pneumoniae pneumonia.
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PMID:Evaluation of LBM415 (NVP PDF-713), a novel peptide deformylase inhibitor, for treatment of experimental Mycoplasma pneumoniae pneumonia. 1618 89


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