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)

Human hepatocellular carcinoma (HCC) cell lines, HEP-G2, J5, and SK-HEP-1, which differ in their differentiation status, were compared for their trans-activating activities after treatment with cytokines or 12-O-tetradecanoylphorbol-13-acetate (TPA). These cells were transfected with a long terminal repeat (LTR) which was derived from human immunodeficiency virus type 1 (HIV-1) and ligated to chloramphenicol acetyl transferase (CAT) gene. After treatment with interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), interferon-gamma (IFN-gamma), or TPA, they exhibited various degrees of enhancement of transactivation. The well differentiated HEP-G2 cells exhibited the highest degree of enhancement with these agents, while the poorly differentiated SK-HEP-1 cells showed no enhancement with cytokines and slight enhancement with TPA. The J5 cells, which were intermediate in their status of differentiation, showed a moderate degree of enhancement with cytokines and TPA. These results suggest that HCC cells at different stages of differentiation may produce different levels of cellular transacting factors activated by each of these agents. To map the cytokine response elements (CREs) in the HIV-1-LTR, HEP-G2 cells were transfected with nested series of 5' deletion mutants of HIV-1-LTR and treated with each of these cytokines. It was found that not only the degrees but also the patterns of enhancement varied depending upon the presence of positive or negative regulatory sequences in HIV-1-LTR, and that the NF-kappa B sequence played an important role, either by itself or in conjunction with the 5'-proximal response elements (REs) to interact with cellular trans-activating factors elicited by the cascade of transduction responses to cytokines. Despite the presence of promoters including kappa B and IFN-gamma RE as well as IL-6RE sequence in HIV-1-LTR-transfected cells, the poorly differentiated SK-HEP-1 cells showed no enhancement of transactivation by these cytokines, suggesting the lack of receptors or activity of some signal transduction factors which are present in well differentiated HEP-G2 and moderately differentiated J5 cells.
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PMID:Cytokine regulation of HIV-1 LTR transactivation in human hepatocellular carcinoma cell lines. 762 43

We have previously shown that a ribozyme directed against human interleukin-6 (IL-6) mRNA is efficient in vivo, despite its poor activity in vitro on full-length IL-6 mRNA. We compared the effect of the nucleocapsid protein of HIV-1 (NCp7) on the ribozyme cleavage reaction of a long (1041 nt) and a short (19 nt) substrate IL-6 RNA in vitro. At a one to five molar ratio of the long substrate to ribozyme, almost no cleavage is observed after 30 min at 37 degrees C. The NCp7 protein significantly increases the catalytic activity of the ribozyme on this substrate (from 0 to 53% after 7 min at 37 degrees C), but not on the short one. A kinetic analysis of single turnover reactions performed with ribozyme in at least fivefold molar excess over substrate also lead to a stimulation (70-fold) of the reaction rate with long substrate, but not with the shorter one. Preferential increases of the catalytic activity on the long substrate suggests that the NCp7 protein prevents misfolding of RNAs.
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PMID:In vitro NCp7 enhancement of ribozyme-mediated cleavage of full-length human IL-6 mRNA. 766 50

In humans, elevated levels of cytokines are associated with several diseases (including HIV infection and Down Syndrome) that result in developmental abnormalities. Overexpression of interleukin-6 (IL-6) in the central nervous system has been shown to cause extensive neuronal abnormality in mice that becomes more evident with maturation. However, it is difficult to separate direct effects of IL-6 on the developing neurons of an intact animal from indirect effects involving effects on other cell types that possess cytokine receptors, such as microglia and astrocytes. We have found that IL-6 treatment of rat cerebellar granule neurons developing in the absence of other cell types in culture results in the persistence of large, depolarization or neurotransmitter-induced calcium transients, that are normally observed only in immature neurons. The cause of this appears to be the persistence of a calcium-induced calcium release (CICR) component of the calcium response to stimulation. This basic abnormality in neuronal development may contribute to the developmental abnormalities associated with human syndromes that involve elevated cytokine levels.
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PMID:Cerebellar granule neurons develop elevated calcium responses when treated with interleukin-6 in culture. 775 67

Monocytes of healthy donors were infected with HIV1 in vitro: 14-21 days after infection 50-70% of the cells produced p24 HIV1 antigen as detected with anti-p24 immunostaining; infected cultures showed enhanced secretion of interleukin-6 (IL6), interleukin-8 (IL8) and tumour necrosis factor alpha (TNF-alpha). The expression of cytokines on the single-cell level was further analysed by in situ hybridization using nonradioactive digoxigenin for detection. HIV1 (p24+) -producing cells were compared with non-HIV (p24-) -producing cells. All morphological subtypes of macrophages showed HIV production; no difference in cytokine expression was observed. Immunocytochemistry of HIV-infected and uninfected cultures also showed no difference in the pattern of IL1-beta, IL6, IL8 and TNF-alpha protein expression in the cells.
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PMID:Cytokine expression of HIV-infected monocytes/macrophages at the single-cell level. 780 Sep 45

Human monocyte-derived macrophages (MDM) were infected with the viral strain HIV1/Ba-L and with the clinical isolates HIV1/DAS and HIV1/PAR. Kinetics of tumour necrosis factor alpha (TNF alpha) and interleukin-6 (IL6) production were investigated for 28 days after infection. At the early stages of infection we observed significant TNF alpha and IL6 secretion 2 to 10 h after infection, whatever the viral strain we used. During the late events of MDM infection, TNF alpha and IL6 were detected over 16 to 21 days following HIV1 infection, at the time of high viral replication. Pretreatment of MDM with a TNF alpha synthesis inhibitor, RP 55778, 4 h prior to HIV infection induced a modified cytokine pattern during the first ten hours of infection: TNF alpha production was totally inhibited despite comparable amounts of IL6. At the late phases of the cell culture, a decrease in magnitude of both viral and cytokine production as well as a delay in the appearance of reverse transcriptase activity and cytokine secretion peaks were observed in RP-55778-pretreated and HIV1-infected MDM cultures. Similar results were obtained after pretreatment of HIV1/DAS-infected MDM cultures with an anti-TNF alpha monoclonal antibody.
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PMID:Treatment of human monocyte-derived macrophages with a TNF alpha synthesis inhibitor prior to HIV1 infection: consequences on cytokine production and viral replication. 780 Sep 46

In this study we evaluated the effect of human immunodeficiency virus type 1 (HIV-1) recombinant Tat protein on mRNA expression and protein synthesis of two inflammatory cytokines-interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-beta 1)-by peripheral blood (PB) monocytes. Whereas maximal levels of IL-6 protein were recovered in PB monocyte culture supernatants after 24-48 h from the addition of 1 micrograms/ml of recombinant Tat, TGF-beta 1 showed a slower and progressive increase, reaching maximal levels only after 72-96 h of culture. Consistently, the analysis of the steady-state levels of mRNA showed a sharp increase of IL-6 mRNA expression after 24h of culture, with a slow decline thereafter. On the other hand, TGF-beta 1 mRNA expression showed a slow increase only after 72-96 h of culture. Moreover, IL-6 appeared involved in the up-regulation of TGF-beta 1, because the addition of a neutralizing anti-IL-6 antibody to Tat-treated PB monocyte cultures significantly reduced the amounts of TGF-beta 1 recovered in the culture supernatants after 96 h. The present demonstration that HIV-1 Tat protein directly up-regulates IL-6 expression and stimulates TGF-beta 1 production both directly and indirectly, through early IL-6 production, could have important implications in the pathogenesis of HIV-1 disease.
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PMID:Recombinant human immunodeficiency virus type-1 (HIV-1) Tat protein sequentially up-regulates IL-6 and TGF-beta 1 mRNA expression and protein synthesis in peripheral blood monocytes. 780 68

Organisms belonging to the Mycobacterium avium complex (MAC) are common pathogens in immunosuppressed and AIDS patients. This paper reviews the role of cytokines in the pathogenesis of MAC infection. MAC organisms mainly infect monocytes and macrophages, and the effect of HIV infection on susceptibility of macrophages to MAC infection is largely unknown. Both GM-CSF and tumour necrosis factor-alpha can induce mycobacteriostatic/mycobactericidal activity in MAC-infected macrophages. The activity of interferon-gamma on mycobacterial infection appears to be dependent on the type of macrophage: in murine peritoneal and human monocyte-derived macrophages, interferon-gamma does not inhibit the intracellular growth of MAC, whereas in intestinal macrophages interferon-gamma results in inhibition of MAC. Transforming growth factor-beta 1, interleukin-10 and interleukin-6 have all been shown to counteract the immunoactivating cytokines and MAC survival may be due to induction of these inhibitory cytokines within the macrophage. GM-CSF has been given to patients with disseminated MAC infection. Isolated macrophages from these patients demonstrated increased superoxide anion production and enhanced mycobacteriostatic/cidal activity compared with macrophages isolated from the same patients before GM-CSF treatment. These results suggest that GM-CSF may have potential in the treatment of MAC infection.
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PMID:Potential role of cytokines in disseminated mycobacterial infections. 787 49

We recently reported clonal human immunodeficiency virus (HIV involvement in four acquired immune deficiency syndrome (AIDS)-associated non-B-cell lymphoproliferations. In three of these cases HIV expression was localized to tumor-associated macrophages. Because one of the cases had a major component involved in angioproliferation, we speculated that some form of Kaposi's sarcoma (KS), which also has a major component of angioproliferation, might be involved clonally with HIV. The current study is an evaluation of four cases of KS and control tissues taken from four patients who died with complications of HIV disease. With use of the inverse polymerase chain reaction technique to identify clonal forms of HIV, a clonal form of HIV was found in one of four KS cases. The HIV-positive tumor was an early KS lesion of the bowel, and uninvolved bowel from the same patient showed no clonal HIV. Immunohistochemical analysis demonstrated the presence of prominent HIV-expressing macrophages that also coexpressed high levels of HIV tat, basic fibroblast growth factor, and interleukin-6. These data provide evidence for a pathogenic process termed "sequential neoplasia," wherein a clonal macrophage provides a growth factor milieu stimulating the proliferation of a responder cell population that ultimately becomes autonomous. In the current case, the macrophages expressing HIV were located adjacent to the KS tumor tissue and were found to be producing known KS growth factors. The absence of finding clonal HIV in three more advanced KS lesions suggests that the clonal macrophage may be required only for early pathogenesis and that sequential neoplastic changes occurring in the endothelial cells gave rise to autonomous KS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of a clonal form of HIV in early Kaposi's sarcoma: evidence for a novel model of oncogenesis, "sequential neoplasia". 788 3

Human cytomegalovirus (HCMV) and human immunodeficiency virus type 1 (HIV-1) may interact in the pathogenesis of AIDS. The placental syncytiotrophoblast layer serves as the first line of defense of the fetus against viruses. We analyzed the patterns of replication of HIV-1 and HCMV in singly an dually infected human term syncytiotrophoblast cells cultured in vitro. Syncytiotrophoblast cells exhibited restricted permissiveness for HIV-1, while HCMV replication was restricted at the level of immediate-early and early gene products in the singly infected cells. We found that the syncytiotrophoblasts as an overlapping cell population could be coinfected with HIV-1 and HCMV. HIV-1 replication was markedly upregulated by previous or simultaneous infection of the cells with HCMV, whereas prior HIV-1 infection of the cells converted HCMV infection from a nonpermissive to a permissive one. No simultaneous enhancement of HCMV and HIV-1 expression was observed in the dually infected cell cultures. Major immediate-early proteins of HCMV were necessary for enhancement of HIV-1 replication, and interleukin-6 production induced by HCMV and further increased by replicating HIV-1 synergized with these proteins to produce this effect. Permissive replication cycle of HCMV was induced by the HIV-1 tat gene product. We were unable to detect HIV-1 (HCMV) or HCMV (HIV-1) pseudotypes in supernatant fluids from dually infected cell cultures. Our results suggest that interactions between HIV-1 and HCMV in coinfected syncytiotrophoblast cells may contribute to the transplacental transmission of both viruses.
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PMID:Interactions between human immunodeficiency virus type 1 and human cytomegalovirus in human term syncytiotrophoblast cells coinfected with both viruses. 788 69

Human immunodeficiency virus infection is associated with the development of focal segmental glomerulosclerosis (FSGS). The majority of these patients with renal disease, however, are also cocaine abusers, but it is unknown what role cocaine may play in the development of focal segmental glomerulosclerosis. We undertook the present study to determine in vitro whether cocaine can modulate mesangial cell (MC) proliferation, a process believed to be a precursor to the development of glomerulosclerosis, either directly or indirectly via interaction with macrophages (M phi). Cocaine alone was not found to alter significantly either MC number or MC [3H]thymidine incorporation. However, when MC were incubated with secretory products collected from M phi preincubated with standard medium or medium containing cocaine, MC proliferation was found to be significantly enhanced with secretory products from M phi preincubated with cocaine in both serum-free (P < .001) and serum-stimulated conditions (P < .001). The effect of cocaine was found to be concentration-related. Pretreatment of macrophage secretory products from cocaine-treated M phi with neutralizing antibodies to transforming growth factor-beta significantly augmented the mitogenic effect of cocaine macrophage secretory products, and neutralizing antibodies to interleukin-6 significantly attenuated this effect. Direct incubation of MC with transforming growth factor-beta and interleukin-6 caused significant suppression and augmentation of MC proliferation, respectively. These data suggest that cocaine can modulate MC proliferation via interaction with M phi and that interleukin-6 and transforming growth factor-beta participate in this modulating effect. These results support a potential role for cocaine in the development of focal segmental glomerulosclerosis in patients with human immunodeficiency virus infection.
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PMID:Cocaine interacts with macrophages to modulate mesangial cell proliferation. 796 30


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