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

Experimental studies show the unique aspects of cytokines profiles in various inflammatory diseases of the lung lead to different clinical manifestations. To elucidate the potential role of cytokines in the pathogenesis of bronchial asthma, plasma interleukins-1 beta, interleukin-6, interferon-gamma and tumour necrosis factor-alpha were measured in 32 asthmatics during an onset of acute asthma. Nine healthy volunteers were included as controls. Cytokine levels were measured by using commercially available ELISA kits. Our results showed that except for interleukin-6, increased concentrations of cytokines were not detected in the controls. Detectable concentrations of IL-6 and TNF-alpha were more common in patients than in controls. However, Interferon-gamma concentrations were below the threshold of detection in both patient and control groups. In conclusions, our results suggest that IL-6 and TNF-alpha are involved during the onset of an acute attack of asthma once the threshold limit has been passed. Hence, these two cytokines are important markers of the inflammatory components of acute asthma.
 ...
PMID:Role of circulating inflammatory cytokines in patients during an acute attack of bronchial asthma. 972 79

The primary biologic roles of C1 inhibitor (C1-INH) are the regulation of activation of the classical complement pathway and of the contact system of kinin formation. Heterozygosity for deficiency or dysfunction of C1-INH results in hereditary angioedema (HAE). This deficiency results in loss of homeostasis with unregulated complement and contact system activation. Due to the consequent C1-INH consumption, plasma levels of C1-INH in patients with HAE are decreased below 50% of normal. In addition, diminished synthesis contributes to the lowered levels in some patients. The hepatocyte is the primary source of C1-INH, although a number of other cell types, including peripheral blood monocytes, microglial cells, fibroblasts, endothelial cells, the placenta, and megakaryocytes also synthesize and secrete the protein both in vivo and in vitro. Interferon-gamma and alpha (IFN), colony stimulating factor-1, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) all induce C1-INH synthesis in a variety of cell types. The IFN-response elements in the 5'-flanking region and in the first intron have been partially characterized, as have several of the promoter elements that direct basal transcription of the gene. However, although androgen therapy, in vivo, results in an increase in C1-INH plasma levels, a direct effect of androgens on C1-INH synthesis has not been convincingly demonstrated. Although the C1-INH gene contains a potential glucocorticoid/androgen response element, this element does not appear to respond to androgen. Continued analysis of the transcriptional regulation of the C1-INH gene may lead to new approaches to therapy of HAE.
 ...
PMID:Regulation of C1 inhibitor synthesis. 977 21

The regulation of C1q expression was examined in the human monocytic cell line THP-1. Since these cells can be differentiated into cells with macrophage properties and induced to express C1q, they were used as models for mature human monocyte/macrophages and indirectly microglia. Interferon-gamma (IFN-gamma) and the anti-inflammatory steroid agents dexamethasone and prednisone were powerful stimulators of C1q production, alone or in combination. Interleukin-6 (IL-6) and lipopolysaccharide (LPS) also had significant stimulatory activity. Phorbol myristate acetate, a protein kinase C activator, reduced C1q expression. Four additional classes of pharmacological agents were tested for their effect on C1q secretion. Tacrine, but not indomethacin, cimetidine, or propentofylline, showed activity in inhibiting C1q secretion by IFN-gamma treated THP-1-derived macrophages.
 ...
PMID:Expression and regulation of complement C1q by human THP-1-derived macrophages. 1032 18

The purpose of this study was to determine if the immunocompatibility of an allogeneic living skin equivalent (LSE) would be affected by cytokines that would be potentially present at the wound site. Specifically, the ability of interleukin-1alpha (IL-1a), interleukin-6 (IL-6), or interleukin-12 (IL-12) to induce an allogeneic T cell response to "nonprofessional" antigen presenting cells (APC) was investigated in this series of experiments. Since cytokine concentrations at the wound site can vary greatly, recombinant IL-1a, IL-6, and IL-12 were used over a wide range of concentrations. These cytokines were either added directly to a mixed lymphocyte reaction (MLR) culture system or used to pretreat APC prior to use in the MLR culture. The addition of IL-12, IL-1alpha, or IL-6 into an MLR was examined as a possible means of providing the necessary costimulatory signal for functionally deficient APC, such as human keratinocytes (HK) and dermal fibroblasts (HF). While the results show that IL-1a and IL-12 can significantly augment a primary allogeneic response against appropriately equipped antigen presenting cells, the same was not true for HK or HF. Further experiments showed that pretreatment of HK, HF, or human umbilical vein endothelial cells (HUVEC) with Interferon-gamma (IFNgamma) and either IL-12, IL1alpha, or IL-6 had no significant affect on their ability to present alloantigen to immune-reactive T lymphocytes over IFNgamma-treatment alone. The data suggest that exposure of HK or HF to IL-1alpha, IL-6, or IL-12 in combination with IFNgamma does not provide the additional signal(s) required by these cells to effectively present alloantigen to unprimed T cells. The data suggests that exposure to these immunoregulatory cytokines in the wound bed would be unlikely to affect the immunocompatibility of the LSE.
 ...
PMID:Effects of immunoregulatory cytokines on the immunogenic potential of the cellular components of a bilayered living skin equivalent. 1035 23

Periprosthetic membranes commonly observed at sites of total joint implant loosening exhibit abundant macrophages and particulate debris. Macrophages phagocytose orthopedic debris and release the pro-inflammatory mediators interleukin-1, interleukin-6, tumor necrosis factor-alpha, and prostaglandin E2. In addition, other immunologic agents, such as interferon-gamma, are present in tissues harvested from the bone-implant interface of failed orthopedic implants. The present study examined the effects of interferon-gamma on polymethylmethacrylate (PMMA) particle-challenged monocyte/macrophages in vitro. The effects of interferon-gamma were determined by measuring interleukin-6 and tumor necrosis factor-alpha release by primary human monocyte/macrophages following exposure to PMMA particles. Exposure of the monocyte/macrophages to PMMA particles resulted in a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha at 48 h. The interleukin-6 release in response to PMMA particle challenge was stimulated by 76% and 127% in the presence of 1.0 and 10.0 ng/mL of interferon-gamma, respectively. Interferon-gamma challenge alone did not alter interleukin-6 release relative to controls. In contrast to interleukin-6, interferon-gamma challenge stimulated tumor necrosis factor-alpha release in a dose-dependent manner. In the presence of particles, addition of 1.0 and 10.0 ng/mL of interferon-gamma resulted in 17% and 171% increases in the levels of tumor necrosis factor-alpha release, respectively, relative to cultures challenged solely with particles. Blocking antibody to IFN-gamma inhibited the effect of IFN-gamma on particle-induced interleukin-6 and tumor necrosis factor-alpha release. The data presented in this study demonstrate that the immunologic modulator interferon-gamma exacerbates monocyte/macrophage release of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in response to PMMA particle challenge in vitro.
 ...
PMID:Interferon-gamma exacerbates polymethylmethacrylate particle-induced interleukin-6 release by human monocyte/macrophages in vitro. 1040 Aug 74

Kaposi's sarcoma (KS) is a complex proliferative lesion long suspected of being dependent on exogenous paracrine signaling molecules to stimulate its proliferative, angiogenic, and inflammatory components. In particular, both clinical and experimental observations have pointed to a potential role for inflammatory cytokines as permissive factors for KS development, but KS pathogenesis is also critically dependent on infection by an exogenous herpesvirus, the KS-associated herpesvirus (KSHV). To examine the possible links between inflammatory cytokines and KSHV replication, we tested for the ability of such cytokines to induce lytic viral reactivation in the latently infected BCBL-1 cell line. Interferon-gamma consistently activated KSHV replication, whereas tumor necrosis factor, interleukin-1, interleukin-2, interleukin-6, granulocyte-macrophage colony stimulating factor, and basic fibroblast growth factor did not. Glucocorticoids also failed to induce lytic KSHV growth in these cells, but ionomycin, a calcium ionophore, induced replication and strongly augmented the known inductive effects of phorbol esters. Interferon-alpha had a dose-dependent inhibitory effect on KSHV induction by ionomycin. The identification of interferon-gamma as an activator and interferon-alpha as an inhibitor of KSHV induction in vitro correlates well with in vivo observations and demonstrates for the first time that inflammatory cytokines can directly modulate KSHV replication.
 ...
PMID:Inflammatory cytokines and the reactivation of Kaposi's sarcoma-associated herpesvirus lytic replication. 1061 56

In the present study the human monoblast cell line U937 has been used as a model to study the function of human mononuclear phagocytes in asthma. The kinetics of the production of eicosanoids and cytokines, which are thought to play a role in the pathogenesis of asthma, were studied. In addition, the effects of glucocorticosteroids were investigated, as these drugs are of great importance for the treatment of asthmatic patients. After stimulation with phorbol-12 myristate acetate (PMA) for 24 h, U937 cells were cultured in the absence or presence of lipopolysaccharide (LPS: 1 and 5 microg ml(-1)) and glucocorticosteroids (budesonide, fluticasone propionate and prednisolone: 10(-11), 10(-9) and 10(-7) M) for 96 h. The production of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) gradually increased in time after stimulation with LPS, whereas the transient production of tumor necrosis factor alpha (TNF-alpha) reached its maximum between 6 and 12 h. Interferon-gamma (IFN-gamma), interleukin-10 (IL-10) and leukotriene B4 (LTB4) were not detectable. All three glucocorticosteroids (budesonide, fluticasone propionate and prednisolone) completely inhibited the production of both eicosanoids and cytokines. The production of eicosanoids was more sensitive to these glucocorticoids than the production of cytokines. The observed differences in the kinetics of the production of eicosanoids and cytokines stress the importance of time course experiments in studies on the effect of drugs on mononuclear cells.
 ...
PMID:Time dependent production of cytokines and eicosanoids by human monocytic leukaemia U937 cells; effects of glucocorticosteroids. 1070 77

In a preliminary study the hypothesis was tested that cytokine profiles in peripheral blood were higher in women with deep infiltrating endometriosis and cytokine profiles in peritoneal fluid were higher in women with superficial endometriosis. Thirteen women of reproductive age having laparoscopy for infertility (n=9), pain (n=3) or combined pain and infertility (n=1). Peripheral blood and peritoneal fluid were obtained and analyzed for Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-10 (IL-10), Transforming Growth Factor-betal (TGFbeta1), and Interferon-gamma (IFN-gamma). No significant cytokine differences were observed in either peritoneal fluid or peripheral blood between IL-6, TGFbeta1, IFNgamma, TNF-alpha and IL-10 of women with superficial endometriosis (n=7) and women with deeply infiltrating endometriosis (n=6). The results of this preliminary study do not show significant differences in peripheral blood and peritoneal fluid cytokine levels between women with deep infiltrating endometriosis compared to women with superficial disease. Future studies with increased sample size are required to either confirm or refute these preliminary findings.
 ...
PMID:Cytokine profiles in autologous peritoneal fluid and peripheral blood of women with deep and superficial endometriosis. 1132 93

Neurons express proteins of the classical complement pathway, including C9. Both the mRNA and protein levels for C9 are sharply upregulated in brain areas affected by Alzheimer's disease (AD). Since little is known about the signals that are responsible for this upregulation, we evaluated in human SH-SY5Y neuroblastoma cells the factors which stimulate C9 production. Interferon-gamma, phorbol myristate acetate and interleukin-6 all stimulated C9 mRNA expression but the inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, as well as the anaphylatoxin C5a and the bacterial lipopolysaccharide, were ineffective. Immunohistochemical analysis of postmortem human brains for C9 protein demonstrated its presence in many cortical pyramidal neurons in AD, Down's syndrome, the parkinsonism dementia complex of Guam and pallido-ponto-nigral degeneration, as well as in thalamic neurons of progressive supranuclear palsy and ballooned neurons of Pick's disease. Since C9 is required for the membrane attack complex of complement to become functional, interfering with signaling pathways that stimulate its production could offer new therapeutic strategies for treating various neurodegenerative disorders.
 ...
PMID:Induction of complement C9 messenger RNAs in human neuronal cells by inflammatory stimuli: relevance to neurodegenerative disorders. 1140 58

Mononuclear phagocytes play a pivotal role in the progression of septic shock by producing tumor necrosis factor-alpha (TNF-alpha) and other inflammatory mediators in response to lipopolysaccharide (LPS) from Gram-negative bacteria. Our previous studies have shown monocyte and macrophage activation correlate with changes in membrane phospholipid composition, mediated by acyltransferases. Interferon-gamma (IFN-gamma), which activates and primes these cells for enhanced inflammatory responses to LPS, was found to selectively activate lysophosphatidylcholine acyltransferase (LPCAT) (P < 0.05) but not lysophosphatidic acid acyltransferase (LPAAT) activity. When used to prime the human monocytic cell line MonoMac 6, the production of TNF-alpha and interleukin-6 (IL-6) was approximately five times greater in cells primed with IFN-gamma than unprimed cells. Two LPCAT inhibitors SK&F 98625 (diethyl 7-(3,4,5-triphenyl-2-oxo2,3-dihydro-imidazole-1-yl)heptane phosphonate) and YM 50201 (3-hydroxyethyl 5,3'-thiophenyl pyridine) strongly inhibited (up to 90%) TNF-alpha and IL-6 production in response to LPS in both unprimed MonoMac-6 cells and in cells primed with IFN-gamma. In similar experiments, these inhibitors also substantially decreased the response of both primed and unprimed peripheral blood mononuclear cells to LPS. Sequence-based amplification methods showed that SK&F 98625 inhibited TNF-alpha production by decreasing TNF-alpha mRNA levels in MonoMac-6 cells. Taken together, the data from these studies suggest that LPCAT is a key enzyme in both the pathways of activation (priming) and the inflammatory response to LPS in monocytes.
 ...
PMID:Acylation of lysophosphatidylcholine plays a key role in the response of monocytes to lipopolysaccharide. 1282 48


<< Previous 1 2 3 4 Next >>