UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1, tumour necrosis factor-alpha and interleukin-6 are considered to be major mediators of inflammatory processes. In the present study, cytokine gene transcription was detected by the polymerase chain reaction technique during cutaneous and intraperitoneal infection with herpes simplex virus-1. Epidermal cell suspensions obtained from mice infected with herpes simplex virus-1 in the ear pinna were enriched or depleted in Langerhans cells by immunomagnetic fractionation. Herpes simplex virus-1 infection in the skin was found to induce interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene transcription in keratinocytes at 24 hours post-infection. Gene transcription declined by 48 hours post-infection. Induction of interleukin-1 beta and tumour necrosis factor-alpha but not of IL-6 gene transcription was detected in Langerhans cells obtained from infected mice at 24 hours post-infection. In order to study cytokine gene transcription during intraperitoneal infection with herpes simplex virus-1, peritoneal exudate cells were obtained from infected mice. Maximal levels of interleukin-1 beta, tumour necrosis factor-alpha, and interleukin-6 mRNA were found in peritoneal exudate cells 6 hours after infection. RNA transcription declined at 24 hours post-infection and was no longer detectable at 48 hours post-infection. Since the higher susceptibility of newborn mice to intraperitoneal herpes simplex virus-1 infection has been suggested to be related to defective cytokine production, cytokine gene transcription was compared in peritoneal exudate cells obtained from infected newborn and adult mice. No significant differences in interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene expression were observed in peritoneal exudate cells obtained from newborn mice as compared with adult mice. In conclusion, cutaneous and intraperitoneal infection with herpes simplex virus-1 induces interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene transcription in epidermal and peritoneal exudate cells.
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PMID:Detection of IL-1 beta, TNF-alpha, and IL-6 gene transcription by the polymerase chain reaction in keratinocytes, Langerhans cells and peritoneal exudate cells during infection with herpes simplex virus-1. 132 63

Monocytes treated with interferon-alpha (IFN-alpha) at virus challenge show no evidence of human immunodeficiency virus (HIV) infection: no p24 antigen or reverse transcriptase (RT) activity, no viral mRNA and no proviral DNA. Levels of p24 antigen and RT activity in monocytes infected with HIV 1-3 weeks before IFN-alpha treatment gradually decrease to baseline. HIV-induced cytopathic changes are markedly reduced, as are levels of HIV mRNA: the frequency of productively infected cells is less than or equal to 1%. But, levels of proviral DNA in the IFN-alpha-treated and control HIV-infected cells are indistinguishable, and remain so through 3 weeks. Large quantities of proviral DNA in IFN-alpha-treated cells with little active transcription suggest true microbiological latency. The major potential source for IFN-alpha in HIV-infected patients is the macrophage. With any of 15 virus isolates, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, IFN-omega or IFN-beta are not detected nor the mRNA expressed in HIV-infected or uninfected monocytes. Both uninfected and HIV-infected monocytes produce high levels of these cytokines after treatment with synthetic double-stranded RNA (poly-I:C). Uninfected monocytes also produce high levels of IFN-alpha after treatment with Poly-I:C, Newcastle disease virus or herpes simplex virus. In marked contrast, HIV-infected monocytes express no IFN-alpha activity or mRNA before or after treatment with any of these agents. The markedly diminished capacity of HIV-infected monocyte to produce IFN-alpha reflects a specific transcriptional block and may be an adaptive mechanism of virus to alter basic microbicidal functions of this cell.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of cytokine and viral gene expression in monocytes infected with the human immunodeficiency virus. 188 15

To identify viral antigens, the types of infiltrating mononuclear cells and cytokine bearing cells, the frozen brain tissue sections form a patient with herpes simplex encephalitis who died on 12th hospital days, were examined by immunocytochemistry methods and combined immunocytochemistry and in situ hybridization. The avidin-biotin peroxidase complex (ABC) techniques were applied for the detection of antigens. All monoclonal antibodies to Leu series and polyclonal antisera to lymphotoxin (LT), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) were purchased form Becton Dickinson Co., and Genzyme Co., (USA) respectively. A large number of neurons and glial cells staining positively HSV-1 antigens were found in the gray matter. Moreover, although a moderate number of HLA-DR (Ia) positive cells were found in the parenchyma, there were few cells displaying positively for Leu-3a, Leu-2a and Leu-7 respectively. To evaluate the number of positive cells appeared in the brain tissues, Leu stain for 4, 2a, 3a, 7, 12 and HLA-DR demonstrated 1.6%, 0.4%, 0.9%, 0.7% and 10% respectively. In addition, numerous number of IFN-gamma positive cells were detected around the lesion and randomly distributed thoroughly the lesion. IL-6 positive cells and LT positive cells were also similar in distribution to IFN-gamma positive cells. Moreover, in simultaneous detection of HLA-DR and HSV-1 mRNA by the combined immunocytochemistry and in situ hybridization, there were seen glial cells staining positively for HLA-DR (Ia) and several cells with mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The detection and quantitative analysis of viral antigens, infiltrating mononuclear cells, IFN-gamma, LT and IL-6 bearing cells in the frozen brain tissue sections from a patient with herpes simplex encephalitis by immunocytochemistry]. 216 12

Kaposi's sarcoma (KS) is a multicentric neoplasia of microvascular origin arising during development of immunodeficiency in human immunodeficiency virus (HIV)-infected individuals. More than 130 patients with HIV-associated KS (98% male homosexuals; median age, 35 years) have been diagnosed at the Department of Dermatology, University Medical Center Steglitz, Berlin, during the years 1982-1992. Mucocutaneous and visceral involvement was a common finding in patients with HIV-associated KS, increasing from 39% at the first visit to 65% at the last observation. In 90% of the patients significant immunosuppression was found (75% had a CD4+ count < 200/mm3) at the time of first diagnosis. However, immunosuppression was not a prerequisite for the development of KS, since the tumor had been diagnosed before severe immunosuppression was present in about 10% of the patients. Significant prognostic predictors for the final outcome were: (a) the degree of immunosuppression, (b) the presence of mucosal and visceral manifestation, and (c) the past history of opportunistic infections. The median survival time was 28 months in KS patients with more than 300 CD4+ lymphocytes (n = 18), but only 14 months in immunosuppressed (less than 300 CD4+ lymphocytes) individuals with KS (n = 70). The median survival time in the entire group evaluated (n = 89 patients) was 17 months after first diagnosis. In 71 HIV-infected individuals who died at the Berlin Department during the last 8 years, disseminated KS was the major direct or indirect cause of death (49% of cases). Therapeutic benefit for KS patients was observed after long-term administration of recombinant interferon alpha (rIFN-alpha; 9-18 million IU s.c. every 2 days) alone or combined with antiretroviral drugs such as zidovudine over several months. Prolongation of survival was found after such treatment modalities in 30%-40% of treated patients. Bleomycin and vincristine and other systemically used cytostatics have also been applied with moderate results. The etiology of HIV-associated KS is still unknown and coinfection with herpes simplex virus (HSV), cytomegalovirus (CMV), or human papillomavirus (HPV) as well as certain growth-stimulating cytokines (transforming growth factors, TGF; tumor necrosis factor alpha, TNF-alpha; interleukin-6, IL-6; tat; vascular endothelial growth factors, VEGF; oncostatin M) produced by HIV-infected cells may be cofactors. Overall, KS was found to be a tumor with high malignant potential, and the median survival times were short.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Kaposi's sarcoma: a reevaluation. 754 Nov 46

Interleukin-6 (IL-6) is an inflammatory cytokine produced in many tissues, including the cornea and trigeminal ganglion. IL-6 acts by binding to its specific receptor, stimulating a cascade of signal proteins that induce the transcription factors NF-IL6 and STAT3. These IL-6-induced transcription factors change cellular gene transcription. Neutralization of IL-6 in vivo inhibits herpes simplex virus type 1 (HSV-1) ocular reactivation in mice. There are IL-6 response elements, possible binding sites of the IL-6 induced transcription factors, within the HSV-1 genome. These IL-6 response elements are concentrated in the inverted repeat regions of the genome, occurring in a non-random fashion in the promoters of the LAT and ICPO genes. Viral constructs containing deletions of IL-6 response elements in the LAT promoter region reactivate at a lower frequency compared with similar constructs lacking such deletions. HSV-1 may have evolved to exploit the relationship between a major inflammatory cytokine, IL-6, and conditions favorable for neuronal reactivation and subsequent replication in the epithelium. Exploring the role of IL-6, its receptor, and induced transcription factors in HSV-1 reactivation is a promising new avenue of research into the mechanism of HSV reactivation.
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PMID:Neuronal reactivation of herpes simplex virus may involve interleukin-6. 947 16

Androstenediol (AED) is a metabolic product of dehydroepiandrosterone (DHEA), an adrenal steroid known to possess immunomodulatory characteristics. The present study was undertaken to assess the efficacy of AED treatment in mice ocularly infected with herpes simplex virus type 1 (HSV-1). The subcutaneous administration of 320 mg/kg AED 4 h prior to viral inoculation was found to enhance the survival of HSV-1-infected mice while lower doses (32.0-100.0 mg/kg) were without effect. However, there were no apparent differences in the viral load in the eye or trigeminal ganglion (TG) 3 or 6 days post infection (p.i.) in vehicle- or AED (320 mg/kg)-treated mice. Likewise, there were no differences in the expression of cytokine or chemokine mRNAs in the eyes or TG early (i.e., 3 days p.i.) following infection. However, by 6 days p.i., there was a significant increase in the expression of the chemokines IP-10, MCP-1, and RANTES and the cytokines interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) in the AED (320 mg/kg)-treated mice compared to vehicle-treated controls as determined by reverse transcription (RT)-polymerase chain reaction (PCR) and quantitative PCR (for IFN-gamma). Likewise, there was a corresponding increase in IFN-gamma and IL-2 but not IL-12 protein in the TG of AED-treated mice 6 days p.i. AED-treatment also induced a rise in splenic natural killer activity in a dose- and time-dependent fashion. Collectively, these results suggest that the protective effect following subcutaneous administration of AED is associated in a rise in selective type 1 cytokines (IL-2 and IFN-gamma) as well as natural killer activity.
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PMID:Increased levels of IFN-gamma in the trigeminal ganglion correlate with protection against HSV-1-induced encephalitis following subcutaneous administration with androstenediol. 972 38

The ability of the pleotropic, proinflammatory cytokine interleukin-6 (IL-6) to affect the replication, latency, and reactivation of herpes simplex virus type 1 (HSV-1) in cell culture and in IL-6 knockout (KO) mice was studied. In initial studies, we found no effect of exogenous IL-6, monoclonal antibodies to IL-6, or monoclonal antibody to the IL-6 coreceptor, gp130, on HSV-1 replication in vitro by plaque assay or reactivation ex vivo by explant cocultivation of latently infected murine trigeminal ganglia (TG). Compared with the wild-type (WT) mice, the IL-6 KO mice were less able to survive an ocular challenge with 10(5) PFU of HSV-1 (McKrae) (40% survival of WT and 7% survival KO mice; P = 0.01). There was a sixfold higher 50% lethal dose of HSV-1 in WT than IL-6 KO mice (1.7 x 10(4) and 2.7 x 10(3) PFU, respectively). No differences were observed in titers of virus recovered from the eyes, TG, or brains or in the rates of virus reactivation by explant cocultivation of TG from latently infected WT or KO mice. Exposure of latently infected mice to UV light resulted in comparable rates of reactivation and in the proportions of WT and KO animals experiencing reactivation. Moreover, quantitative PCR assays showed nearly identical numbers of HSV-1 genomes in latently infected WT and IL-6 KO mice. These studies indicate that while IL-6 plays a role in the protection of mice from lethal HSV infection, it does not substantively influence HSV replication, spread to the nervous system, establishment of latency, or reactivation.
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PMID:Lack of interleukin-6 (IL-6) enhances susceptibility to infection but does not alter latency or reactivation of herpes simplex virus type 1 in IL-6 knockout mice. 1048 64

Inoperable adenocarcinoma in colon or lung shows resistance to conventional anti-cancer therapy. For these cancers, the feasibility of transcriptionally targeted killing of carcinoembryonic antigen (CEA)-producing adenocarcinoma cells was investigated. Adenovirus vectors carrying a CEA promoter to express E. coli lacZ (AdCEALacZ) or herpes simplex thymidine kinase (AdCEATK) were made and their in vitro and in vivo tumoricidal effects on CEA-producing or non-producing colon and lung cancer cells were evaluated. In vitro infection with AdCEALacZ showed significantly higher CEA promoter-driven lacZ expression in CEA-producing adenocarcinoma cells including VMRC-LCD and LoVo than in CEA-non-producing cells. AdCEATK-infected LoVo showed higher sensitivity to ganciclovir than control vector-infected LoVo or AdCEATK-infected HeLa both in vitro and in subcutaneously implanted tumors of nude mice. Moreover, total tumor elimination in vivo was achieved by either pre-infection of as few as 30% of cells comprising tumors or by direct in vivo injection of AdCEATK to pre-established LoVo tumors. In addition, CEA promoter-driven lacZ expression in LoVo cells was enhanced by the addition of interleukin-6 (IL-6) in vitro. These results provide a rationale for CEA-promoter-driven, adenovirus-mediated gene therapy for CEA-producing adenocarcinomas in colon and lung with reduced toxicity to normal cells.
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PMID:Transcriptionally targeted in vivo gene therapy for carcinoembrionic antigen-producing adenocarcinoma. 1059 10

Stress has been shown to modulate an individual's immune system through the release of certain signal molecules such as catecholamines, cytokines and glucocorticoids. These signal molecules can significantly alter the host immune system and leave it susceptible to a primary or recurrent viral infection. Focusing on herpes simplex virus types-1 and -2 as examples, the authors explain how stress-associated immunomodulation can influence the recurrence of herpes simplex viral infections. Specific signal molecules such as epinephrine, interleukin-6, cyclic adenosine monophosphate, glucocorticoids and prostaglandins are upregulated during episodes of acute and chronic stress and have been implicated as effectors of herpes simplex viral reactivation and recurrent disease. The authors suggest that the release of immunomodulating signal molecules due to stress can compromise the host's cellular immune response and trigger herpes simplex viral reactivation.
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PMID:Stress-associated immunomodulation and herpes simplex virus infections. 1135 58

Cytokines play important roles in the clearance of herpes simplex virus (HSV) infections and in virus-induced immunopathology. One cytokine known to contribute to resistance against HSV is interleukin-6 (IL-6). Here we have investigated virus-cell interactions responsible for IL-6 induction by HSV in leukocytes. Both HSV type 1 and type 2 are potent inducers of IL-6, and this phenomenon is augmented in the presence of gamma interferon. The ability to induce IL-6 is dependent on de novo protein synthesis and is sensitive to UV irradiation of the virus. Virus mutants lacking the virion-transactivating protein VP16 or any of the immediate-early proteins ICP0, ICP4, or ICP27 displayed unaltered capacities to induce IL-6. However, wild-type virus was unable to induce IL-6 in a macrophage cell line overexpressing a mutant of double-stranded RNA-activated protein kinase (PKR). This suggests a role for PKR in HSV-induced IL-6 expression. HSV infection led to enhanced binding to the kappaB, CRE, and AP-1 sites of the IL-6 promoter, and inhibitors against NF-kappaB and the p38 kinase strongly reduced accumulation of IL-6 mRNA in infected cells. Moreover, macrophage cell lines expressing dominant negative mutants of IkappaBalpha and p38 responded to HSV-1 infection with reduced IL-6 expression compared to the control-vector-transfected cell line. The results show that induction of IL-6 by HSV in leukocytes is dependent on PKR and cellular signaling through NF-kappaB and a p38-dependent pathway.
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PMID:Requirements for the induction of interleukin-6 by herpes simplex virus-infected leukocytes. 1148 45

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