UNIPROT:P05231 - FACTA Search

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)

The human immunodeficiency virus type 1 (HIV-1) Tat gene, a potent transactivator of viral and cellular genes, has been proposed as a key agent in the pathogenesis of acquired immune deficiency syndrome related disorders, including non-Hodgkin's lymphoma. In cultured cells, the HIV-1 Tat protein can induce the expression of the cytokines interleukin-6 (IL-6) and IL-10, which are known to induce proliferation and differentiation of lymphoid cells. Such alterations in cytokine expression, together with a secondary genetic event, are thought to ultimately lead to oncogenic transformation. To address the influence of Tat on lymphoid development in the context of the whole organism, we produced several transgenic mouse lines that express the Tat gene under the control of an actin promoter. We show here that this promoter directs expression to a variety of sites, including spleen, bone marrow, and lymph nodes. Approximately 25% to 30% of the Tat-transgenic population developed enlarged spleens within 1 year after birth. On histological examination, a significant number of spleens from Tat-transgenic mice exhibited malignant lymphoma of B-cell origin. IgG heavy chain rearrangement confirmed the clonal B-cell nature of these lymphoproliferations. In contrast, T-cell receptor genes exhibited a germline (unrearranged) structure. Reverse transcription polymerase chain reaction analysis of transgenic spleens revealed that mRNA encoding cytokines IL-6 and IL-10 was upregulated, suggesting a possible mechanism for the B-cell expansion in vivo.
...
PMID:Expression of the human immunodeficiency virus-Tat gene in lymphoid tissues of transgenic mice is associated with B-cell lymphoma. 1038 23

To investigate neuropathological processes involved in HIV infection, a longitudinal analysis of central nervous system (CNS) changes was performed using the SIV-infected macaque model. Five animals were studied during the early phase and 13 during the asymptomatic and symptomatic phases. Histopathological analyses were performed on one cerebral fixed hemisphere whereas on the other frozen hemisphere in situ hybridisation, immunohistochemistry and RT-PCR were performed. Viral load was quantified by in situ hybridisation, CD4 and CD8 T cell infiltration by immunohistochemistry and mRNA cytokine expression (IL1beta, IL2, IL6, TNFalpha, IFNgamma and TGF-beta1) by semiquantitative RT-PCR. As reported for HIV-infected humans, the neuropathological analysis of SIV infected animals revealed four distinct lesion profiles: minimal changes, early encephalitis, leukoencephalopathy and encephalitis. No relationship was found between neuropathological findings, numbers of SIV replicating cells and T cell infiltration. CNS infection was found to be an early event characterised by glial activation, an increase in the level of IL1beta, TNFalpha and IL6 mRNA expression. During the asymptomatic and symptomatic phases, IL6 and IL1beta mRNAs increase coincided with gliosis and the development of myelin lesions. The absence of relationship between neuropathological findings and viral load suggests that cerebral lesions are caused by an indirect mechanism. Inflammatory cytokine pattern associated with severe lesions show the key role of glial activation in the SIV neuropathological process.
...
PMID:Viral load and neuropathology in the SIV model. 1041 13

This study assessed glucose tolerance, insulin sensitivity and lipid parameters in HIV-infected patients presenting with lipodystrophy during HAART including protease inhibitors. Fourteen consecutive patients from Rothschild Hospital treated with HAART and presenting with marked facial lipoatrophy were evaluated. A 75 g oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, proinsulin and free fatty acids at T0, 30, 60, 90 and 120 min was performed. Lipid parameters (triglycerides, cholesterol, apolipoproteins A1 and B) were studied as well as nutritional and inflammatory markers (albumin, prealbumin, transferrin, haptoglobin, orosomucoid, C-reactive protein), endocrine and cytokine parameters (thyrotropin, cortisol, leptin, interleukin-6), HIV viral load and CD4-lymphocyte count. These patients were compared with 20 non-lipodystrophic protease inhibitor-treated patients. The measurements performed during OGTT showed that among the 14 lipodystrophic patients, 11 (79%) presented with diabetes (5 patients) or normal glucose tolerance but with insulin resistance (6 patients). This frequency was strikingly different in the group of nonlipodystrophic patients, which included only 4 (20%) presenting with diabetes (1 patient), or impaired glucose tolerance (2 patients), or normal glucose tolerance but with insulin resistance (1 patient). Hypertriglyceridaemia was present in 11 lipodystrophic (79%) versus 7 nonlipodystrophic patients (35%). Nutritional and endocrine measurements were normal. An abnormal processing of proinsulin to insulin was excluded. Thus, lipodystrophy during HAART was associated with diabetes, insulin resistance and hypertriglyceridaemia. Diabetes, diagnosed by basal and/or 120 min-OGTT glycaemia, seems more frequent than previously described. The therapeutic consequences of these results deserve evaluation in clinical trials.
...
PMID:Diabetes, insulin resistance and dyslipidaemia in lipodystrophic HIV-infected patients on highly active antiretroviral therapy (HAART). 1049 91

Human herpesvirus 8 (HHV-8) has been causally linked to Kaposi's sarcoma (KS). There is significant homology between some HHV-8 genes and cellular genes including D-type cyclin (vCYC), G protein coupled receptor (vGCR), macrophage inflammatory proteins (vMIP-I, vMIP-II), bcl-2 (vBCL2), interferon regulatory factor-1 (vIRF1), interleukin-6 (vIL6), and complement-binding protein (vCBP). In this study, we analyzed expression of these viral homologs and HIV-1 Tat by reverse-transcriptase polymerase chain reaction (RT-PCR) coupled with Southern blot hybridization in AIDS-KS (AKS) tissue, classic KS tissue(CKS), and peripheral blood mononuclear cells, and phorbol ester (TPA)-treated and untreated HHV-8 positive lymphoma cells (BCBL1). While vCYC (AKS 6 of 6; CKS 3 of 3), vMIP-I (AKS 5 of 6, CKS 3 of 3), vBCL2 (AKS 6 of 6; CKS 3 of 3), and vIRF1 (AKS 5 of 6, CKS 3 of 3) transcripts were detected in both AKS and CKS, vGCR and HIV-1 Tat were expressed only in AKS samples (vGCR: AKS 3 of 6, CKS 0 of 3; Tat: AKS 4 of 6, CKS 0 of 3). vMIPII, vCBP, and vIL6 expression were not detected in any KS samples. Since vGCR expression is limited to AKS, it is possible that vGCR is activated by HIV-1 Tat. These results suggest that HIV-1 Tat may contribute to AKS pathogenesis through the tumorigenic and angiogenic effects of vGCR.
...
PMID:Differential expression of the HHV-8 vGCR cellular homolog gene in AIDS-associated and classic Kaposi's sarcoma: potential role of HIV-1 Tat. 1066 20

Skeletal muscle tissue from SIV-infected macaques was previously found to contain abnormally high sulfate and low glutathione levels indicative of an excessive cysteine catabolism. We now confirm the peripheral tissue as a site of massive cysteine catabolism in HIV infection and have determined the urinary loss of sulfur per time unit. The comparison of the sulfate concentrations of the arterial and venous blood from the lower extremities of 16 symptomatic HIV+ patients and 18 HIV- control subjects (study 1) revealed (1) that the peripheral tissue of HIV+ patients with or without highly active antiretroviral therapy (HAART) releases large amounts of sulfate and (2) that plasma sulfate, thioredoxin, and interleukin-6 levels are elevated in these patients. A complementary investigation of 64 asymptomatic HIV+ patients and 65 HIV- subjects (study 2) revealed increased plasma sulfate levels in the asymptomatic patients. The analysis of the daily urinary excretion of sulfate and urea of another group of 19 HIV+ patients and 22 healthy HIV- subjects (study 3) confirmed (1) that HIV+ patients experience a massive loss of sulfur and (2) that this loss is not ameliorated by HAART. The sulfur loss of asymptomatic patients was equivalent to a mean loss of about 10 g of cysteine per day. If extrapolated, this would correspond to an alarming negative balance of approximately 2 kg of cysteine per year under the assumption that the normal sulfate excretion equivalent to approximately 3 g of cysteine per day is balanced by a standard Western diet. The abnormally high sulfate/urea ratio suggests that this process drains largely the glutathione pool.
...
PMID:Massive loss of sulfur in HIV infection. 1071 Feb 8

Maintenance of health depends on the ability to respond appropriately to environmental stressors via reciprocal interactions between the body and the brain. In this context, it is well recognized that the pineal hormone melatonin (MLT) plays an important role. T-helper cells bear G-protein-coupled MLT cell membrane receptors and, perhaps, MLT nuclear receptors. Activation of MLT receptors enhances the release of T-helper cell cytokines, such as gamma-interferon and interleukin-2 (IL-2), as well as activation of novel opioid cytokines which crossreact immunologically with both interleukin-4 and dynorphin B. MLT has been reported also to enhance the production of interleukin-1, interleukin-6 and interleukin-12 in human monocytes. These mediators may counteract secondary immunodeficiencies, protect mice against lethal viral and bacterial diseases, synergize with IL-2 against cancer and influence hematopoiesis. Hematopoiesis is influenced by MLT-induced-opioids (MIO) acting on kappa 1-opioid receptors present on bone marrow macrophages. Clinically, MLT could amplify the anti-tumoral activity of low dose IL-2, induce objective tumor regression, and prolong progression-free time and overall survival. MLT seems to be required for the effectiveness of low dose IL-2 in those neoplasias that are generally resistant to IL-2 alone. Similar findings were obtained in a study in which MLT was combined with gamma-interferon in metastatic renal cell carcinoma. In addition, MLT in combination with low-dose IL-2 was able to neutralize the surgery-induced lymphocytopenia in cancer patients. IL-2 treatment in patients results in activation of the immune system and creates the most suitable biological background for MLT. The finding that MLT stimulates IL-12 production from human monocytes only if incubated in presence of IL-2 further supports this concept. On the other hand, high concentrations of MLT have been found in human breast cancer tissue. The MLT concentration, which was 3 orders of magnitude higher than that present in the plasma, correlated positively with good prognostic markers such as estrogen receptor status and nuclear grade. Whether this relates to the immunoneuroendocrine action of MLT remains to be established. Clinical studies are needed on the effect of MLT in combination with IL-2 or other cytokines in cancer patients and viral diseases including HIV-infected patients.
...
PMID:Therapeutic potential of melatonin in immunodeficiency states, viral diseases, and cancer. 1072 Oct 59

Gene therapy is an attractive therapy for hepatocarcinoma, and several approaches have been studied using murine leukemia virus-derived retroviruses. We compared gene transfer efficacy and transgene expression kinetics after transduction of hepatocarcinoma cell lines using enhanced green fluorescent protein (EGFP)-expressing murine leukemia virus-derived retroviral vectors and HIV-derived lentiviral vectors. First, we showed that both retroviral and lentiviral vectors efficiently transduce cycling hepatocarcinoma cell lines in vitro. However, after cell cycle arrest, transduction efficacy remained the same for lentiviral vectors but it decreased by 80% for retroviral vectors. Second, we studied EGFP expression kinetics using lentiviral vectors expressing EGFP under the control of cytomegalovirus (CMV) or phosphoglycerolkinase (PGK) promoter. We show that the CMV promoter allows a stronger EGFP expression than the PGK promoter. However, in contrast to PGK-driven EGFP expression, which persists up to 2 months after transduction, CMV-driven EGFP expression rapidly decreased with time. This phenomenon is due to promoter silencing, and EGFP expression can be restored in transduced cells by using transcription activators such as interleukin-6 or phorbol myristate acetate/ionomycin and, to a lesser extent, the demethylating agent 5'-azacytidine. Altogether, our results suggest that lentiviral vectors, which allow efficient transduction of hepatocarcinoma cell lines with a strong and a sustained expression according to the promoter used, are promising tools for gene therapy of hepatocarcinomas.
...
PMID:Gene transfer to hepatocellular carcinoma: transduction efficacy and transgene expression kinetics by using retroviral and lentiviral vectors. 1102 2

Recent observations have shown two CCAAT/enhancer binding protein (C/EBP) binding sites to be critically important for efficient human immunodeficiency virus type 1 (HIV-1) replication within cells of the monocyte/macrophage lineage, a cell type likely involved in transport of the virus to the brain. Additionally, sequence variation at C/EBP site I, which lies immediately upstream of the distal nuclear factor kappa B site and immediately downstream of a binding site for activating transcription factor (ATF)/cyclic AMP response element binding protein (CREB), has been shown to affect HIV-1 long terminal repeat (LTR) activity. Given that C/EBP proteins have been shown to interact with many other transcription factors including members of the ATF/CREB family, we proceeded to determine whether an adjacent ATF/CREB binding site could affect C/EBP protein binding to C/EBP site I. Electrophoretic mobility shift analyses indicated that selected ATF/CREB site variants assisted in the recruitment of C/EBP proteins to an adjacent, naturally occurring, low-affinity C/EBP site. This biophysical interaction appears to occur via at least two mechanisms. First, low amounts of CREB-1 and C/EBP appear to heterodimerize and bind to a site consisting of a half site from both the ATF/CREB and C/EBP binding sites. In addition, CREB-1 homodimers bind to the ATF/CREB site and recruit C/EBP dimers to their cognate weak binding sites. This interaction is reciprocal, since C/EBP dimer binding to a strong C/EBP site leads to enhanced CREB-1 recruitment to ATF/CREB sites that are weakly bound by CREB. Sequence variation at both C/EBP and ATF/CREB sites affects the molecular interactions involved in mediating both of these mechanisms. Most importantly, sequence variation at the ATF/CREB binding site affected basal LTR activity as well as LTR function following interleukin-6 stimulation, a treatment that leads to increases in C/EBP activation. Thus, HIV-1 LTR ATF/CREB binding site sequence variation may modulate cellular signaling at the viral promoter through the C/EBP pathway.
...
PMID:Interaction between CCAAT/enhancer binding protein and cyclic AMP response element binding protein 1 regulates human immunodeficiency virus type 1 transcription in cells of the monocyte/macrophage lineage. 1116 Jun 83

Expression of a viral interleukin-6 (vIL-6) has been detected in certain Kaposi sarcoma (KS)--associated herpesvirus positive (KSHV(+)) lesions. The release of vIL-6 systemically and its contribution to the pathogenesis of HIV-related malignancies was studied. Serum vIL-6 was detected in 13 (38.2%) of 34 HIV(+) patients with KS, in 6 (85.7%) of 7 HIV(+) patients with primary effusion lymphoma (PEL) and/or multicentric Castleman disease (MCD), and in 18 (60.0%) of 30 HIV(+), mostly homosexual, individuals without KS, MCD, or PEL. By contrast, serum vIL-6 was detected in only 3 (23.1%) of 13 patients with classic KS, 1 (2.5%) of 40 blood donors from the United States, and 4 (19.0%) of 21 blood donors from Italy. Circulating vIL-6 levels were associated with HIV(+) status (P <.0001). However, within the HIV(+) cohort, serum vIL-6 levels were not associated with the occurrence of KSHV-associated malignancies (P =.43). (Blood. 2001;97:2173-2176)
...
PMID:Detection of viral interleukin-6 in Kaposi sarcoma-associated herpesvirus-linked disorders. 1126 89

We studied 15 bone marrow biopsy specimens from patients with human immunodeficiency virus infection for detection of Kaposi sarcoma herpesvirus (KSHV/HHV-8) DNA sequences by a very sensitive and specific polymerase chain reaction (PCR) assay (with 3 different sets of primers). In addition, we used immunohistochemistry with antiviral interleukin-6 (vIL-6) and anti-latent nuclear antigen-1 (LNA-1) antibodies to localize the infected cells on tissue sections. Among the 15 samples, 6 had positive PCR results with the 3 sets of primers (orf26, orf72, orf75). Interestingly, in 2 of these 6 patients (both with Kaposi sarcoma) vIL-6 and LNA-1 were detected in mononuclear lymphoid cells but not in stromal cells of the bone marrow. The detection of vIL-6--positive lymphoid cells in bone marrow suggests a homing for HHV-8--infected elements in this tissue. The local release of vIL-6 may play some role in the plasmacytosis observed in bone marrow in the acquired immunodeficiency syndrome. HUM PATHOL 32:288-291.
...
PMID:Detection and characterization of human herpesvirus-8-infected cells in bone marrow biopsies of human immunodeficiency virus-positive patients. 1127 37

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