Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spontaneous secretion of interleukin 8 (IL-8) was higher in latently infected U1 cells than in acutely infected or uninfected parental U937 cells. However, the induction of IL-8 by various cytokines (IL-1 alpha, TNF-alpha, IL-6, TNF-beta, GM-CSF, IFN-gamma) was significantly reduced in U1 cells. Cytokine modulation of IL-8 production in U937 cells acutely infected with a T cell-tropic strain (IIIB) or monocytotropic strain (ADA) of human immunodeficiency virus 1 (HIV-1) (HIV-1IIIB and HIV-1ADA) was variable and showed strain-specific differences. The obtained results showed that the in vitro induction of IL-8 is impaired in promonocytic cells latently infected with HIV-1 and is differently modulated under acute conditions of infection depending on the IL-8 inducing cytokine and on the infecting virus strain.
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PMID:Cytokine-induced interleukin-8 production is depressed in chronic as opposed to acute human immunodeficiency virus 1 infection of promonocytic cells. 1115 65

The family of NF-kappaB/rel transcription factors regulates a variety of promoters through specific DNA-binding sites. Consistent with the role of NF-kappaB activation as a response to pathogens, it regulates the expression of immune modulating cytokines like interferon-beta3 (IFN-3). Transcriptional regulation of IFN-beta is characterized by strict constitutive repression and virus-mediated activation. A nuclear protein, called NRF (NF-kappaB repressing factor) silences constitutively the IFN-beta3 promoter by binding to the negative regulatory element (NRE). This control is achieved by a direct protein-protein interaction between NRF and proximal bound NF-kappaB factors preventing the transcriptional activation. After viral induction NRF still binds but does not any more exert its specific inhibition. NRE-related sequences found in a number of promoters like those of HIV-1, HTLV-1 and the genes of the IL-2Ralpha and IL-8 constitute functionally related silencer elements which repress the constitutive enhancing activity of NF-kappaB/rel-binding sites from these promoters.
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PMID:NRF, a nuclear inhibitor of NF-kappaB proteins silencing interferon-beta promoter. 1120 93

During the last few years much attention has been paid to the chemokines. Chemokine receptors are necessary to render a target permissive for infection by the human immunodeficiency virus (HIV) and high concentrations of chemokines have been shown to protect against the progression of HIV disease towards death. In the present study, we investigated the capability of strenuous exercise to induce elevated plasma concentrations of the chemokines interleukin (IL)-8, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta. Eight male athletes completed the Copenhagen Marathon 1997. Blood was sampled before, immediately after the run and every 30 min during a 4 h recovery period. Plasma chemokine concentrations were measured using enzyme-linked immunosorbent assays. The IL-8, MIP-1 alpha and MIP-1 beta concentrations all peaked 0.5 h after the run when they were 6.7-fold, 3.5-fold and 4.1-fold increased, respectively. The elevated concentrations of chemokines in plasma after exercise could have implications for HIV-infected individuals; a possibility that needs further investigation.
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PMID:Chemokines are elevated in plasma after strenuous exercise in humans. 1132 Jun 43

Researchers have discovered the co-factor, called fusin, that allows HIV to fuse with and insert its genetic material into a cell. The fusin gene is a member of the gene family that produces G protein-coupled cell receptors, often exploited by other viruses when entering cells. Research found fusin to be a valid antiviral target, but no one knows its natural function. A shortcoming of anti-fusin drugs is that anti-fusin antibodies had no effect on the infection of macrophages. There is circumstantial evidence that fusin is similar to the IL-8 chemokine receptor, which may allow HIV to fuse to macrophages. The discovery of fusin makes development of effective animal models more likely.
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PMID:Viral entry discovery suggests new treatments. 1136 81

C/EBPbeta is a member of a family of leucine zipper transcription factors that are involved in regulating the expression of several cytokines, including IL-1, IL-6, IL-8, TNF, and macrophage-inflammatory protein-1alpha. We identified multiple C/EBPbeta binding sites within the gene for CCR5, suggesting that C/EBPbeta may be involved in its regulation. Transient transfection experiments in both myeloid and lymphoid cells showed an increase in CCR5 promoter-driven green fluorescent protein production in the presence of C/EBPbeta. Deletion analysis identified two C/EBPbeta-responsive regions in the CCR5 gene, one in the promoter region and one at the 3' part of the intron. We provide evidence that, in myeloid cells (U937), C/EBPbeta independently activates CCR5 expression through sites located either in the promoter region or in the intron of the CCR5 gene. In contrast, in lymphoid cells (Jurkat) the presence of the intronic cis-regulatory regions is required for C/EBPbeta-mediated activation. In agreement with the functional data, EMSA demonstrated that in both myeloid and lymphoid cells C/EBPbeta binds specifically to sites present in the intron, whereas interaction with the sites located in the promoter was cell type specific and was detected only in myeloid cells. Analysis of C/EBPbeta in primary PBMCs obtained from HIV-1-infected individuals revealed a significant increase in C/EBPbeta expression. The enhanced C/EBPbeta activity correlated with a higher frequency of circulating CCR5(+) lymphocytes in AIDS patients and with a decline in CD4 lymphocyte numbers. Taken together, these results suggest that C/EBPbeta is an important regulator of CCR5 expression and may play a relevant role in the pathogenesis of HIV disease.
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PMID:CCAAT-enhancer-binding protein beta (C/EBP beta) activates CCR5 promoter: increased C/EBP beta and CCR5 in T lymphocytes from HIV-1-infected individuals. 1146 89

To stimulate transcriptional elongation of HIV-1 genes, the transactivator Tat recruits the positive transcription elongation factor b (P-TEFb) to the initiating RNA polymerase II (RNAPII). We found that the activation of transcription by RelA also depends on P-TEFb. Similar to Tat, RelA activated transcription when tethered to RNA. Moreover, TNF-alpha triggered the recruitment of P-TEFb to the NF-kappaB-regulated IL-8 gene. While the formation of the transcription preinitiation complex (PIC) remained unaffected, DRB, an inhibitor of P-TEFb, prevented RNAPII from elongating on the IL-8 gene. Remarkably, DRB inhibition sensitized cells to TNF-alpha-induced apoptosis. Thus, NF-kappaB requires P-TEFb to stimulate the elongation of transcription and P-TEFb plays an unexpected role in regulating apoptosis.
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PMID:NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. 1154 35

Inflammatory cytokines and human immunodeficiency virus type 1 (HIV-1) gp120 are considered to play an important role in the pathogenesis of HIV-1-associated CNS disorders. These substances are produced predominantly by HIV-1-infected or activated macrophages and microglia in the brain and induce neural cell death. Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have anti-inflammatory, anti-allergic, and immunomodulatory activities in vivo. We previously reported that this compound could inhibit tumor necrosis factor (TNF)-alpha- or phorbol 12-myristate 13-acetate-induced HIV-1 replication in latently infected U1 cells through the inhibition of nuclear factor-kappaB, a potent inducer of HIV-1 gene expression. In the present study, we demonstrated that cepharanthine suppresses the production of inflammatory cytokines and a chemokine, i.e. TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-8, in human monocytic cell cultures, including primary monocyte/macrophage cultures. This effect of cepharanthine was concentration-dependent, and significant suppression was observed at 0.1 microg/mL. Furthermore, the compound also inhibited TNF-alpha- and gp120-induced death of differentiated human neuroblastoma cells at a concentration of 0.04 to 0.2 microg/mL. It penetrates the blood-brain barrier, and a medicine containing cepharanthine as a major component has been used in Japan for the treatment of patients with chronic inflammatory diseases. Thus, cepharanthine should be investigated further for its therapeutic and prophylactic potential in HIV-1-associated CNS disorders.
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PMID:Suppression of cytokine production and neural cell death by the anti-inflammatory alkaloid cepharanthine: a potential agent against HIV-1 encephalopathy. 1155 20

Kaposi's sarcoma (KS) is the most common tumor associated with HIV-1 infection. Here, we report the expression, regulation, and biological effect of interleukin (IL)-8 in KS. AIDS-KS cell lines expressed higher levels of IL-8 than either human umbilical vein endothelial cells (HUVECs), human aortic smooth muscle (AoSM) cells or fibroblast cells (T1). The inflammatory cytokine IL-1beta up-regulated IL-8 expression in a time- and concentration-dependent manner in KS cell lines. IL-8 antisense oligonucleotides specifically reduced IL-8 mRNA and protein levels and inhibited KS cell growth in a dose-dependent manner. In addition, supernatant from a KS cell line induced the growth of HUVECs and angiogenesis in chicken chorioallantoic membrane assays, both of which were inhibited by IL-8 neutralizing antibody. Serum levels of IL-8 were also elevated in KS cases compared with matched controls. Modulation of IL-8 may thus be of therapeutic value in this disease.
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PMID:Interleukin 8 is an autocrine growth factor and a surrogate marker for Kaposi's sarcoma. 1155 81

The revival of thalidomide began shortly after the drug was withdrawn from the market because of its teratogenic properties. Therapeutic effects of thalidomide were found accidentally in leprosy patients with erythema nodosum leprosum (ENL). Subsequent research widened the understanding of the activity of thalidomide, and with improved methodology and the augmented background knowledge of immunology it was possible to interpret the properties of thalidomide more coherently. Effects on tumour necrosis factor-alpha (TNFalpha) release play an important role in the ability of thalidomide to affect the immune system. Alteration of synthesis and release of cytokines such as interleukin (IL)-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 and interferon-gamma is involved in the complex mechanisms of thalidomide. Thalidomide targets leucocytes, endothelial cells and keratinocytes, affecting them in a different manner and at different cellular levels. Changes in the density of adhesion molecules alter leucocyte extravasation and the inflammatory response in the tissue involved. Several mechanisms for the teratogenic action of thalidomide are currently under review, but this mode of action of the drug still remains unclear and we review evidence-based hypotheses for the teratogenicity of thalidomide. Thalidomide shows significant clinical impact in several diseases such as ENL in lepromatous leprosy, chronic graft-versus-host disease, systemic lupus erythematosus, sarcoidosis, aphthous lesions in HIV infection, wasting syndrome in chronic illness, inflammatory bowel disease, multiple myeloma and some solid tumours. In 1998 the US Food and Drug Administration approved thalidomide exclusively for the treatment of ENL, and strict conditions were stipulated for its use in order to prevent teratogenic adverse effects. However, despite the promising findings of thalidomide at the molecular level, namely its anti-TNFalpha properties and its intercalation with DNA, and activity in clinical trials, there is still a great need for more intensive research.
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PMID:Theoretical basis for the activity of thalidomide. 1160 49

Natural killer (NK) cells participate in innate and adaptive immune responses to obligate intracellular pathogens and malignant tumors. Two major NK cell subsets have been identified in humans: CD56(dim) CD16+ and CD56(bright) CD16-. Resting CD56(dim) CD16+ NK cells express CXCR1, CXCR2, CXCR3, CXCR4, and CX3CR1 but no detectable levels of CC chemokine receptors on the cell surface. They migrate vigorously in response to CXCL12 and CXC3L1. In contrast, resting CD56(bright) CD16- NK cells express little CXCR1, CXCR2, and CXC3R1 but high levels of CCR5 and CCR7. Chemotaxis of CD56(bright) CD16- NK cells is stimulated most potently by CCL19, CCL21, CXCL10, CXCL11, and CXCL12. Following activation, NK cells can migrate in response to additional CC and CXC chemokines. Cytolytic activity of NK cells is augmented by CCL2, CCL3, CCL4, CCL5, CCL10, and CXC3L1. Moreover, proliferation of CD56(dim) CD16+ NK cells is costimulated by CCL19 and CCL21. Activated NK cells produce XCL1, CCL1, CCL3, CCL4, CCL5, CCL22, and CXCL8. Chemokines secreted by NK cells may recruit other effector cells during immune responses. Furthermore, CCL3, CCL4, and CCL5 produced by NK cells can inhibit in vitro replication of HIV. CCL3 and CXL10 expression appear to be required for protective NK cell responses in vivo to murine cytomegalovirus or Leishmania major, respectively. Moreover, NK cells participate in the in vivo rejection of transduced tumor cells that produce CCL19 or CCL21. Thus, chemokines appear to play an important role in afferent and efferent NK cell responses to infected and neoplastic cells.
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PMID:Role of chemokines in the biology of natural killer cells. 1181 37


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