Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The establishment of a primary trigeminal ganglion (TG) cell culture latently infected with herpes simplex virus type 1 (HSV-1) has been useful in studying stress-induced reactivation of the latent virus. However, the immune profile of this culture system prior to and after stress has never been established. In the present manuscript, cytokine and chemokine production were measured in primary cultures of TG cells obtained from uninfected and HSV-1 latently infected mice. Supernates from TG cell cultures contained detectable interleukin (IL)-6 but not IL-1beta, IL-2, IL-10, interferon (IFN)-gamma or tumor necrosis factor (TNF)-alpha as determined by ELISA. The basal level of IL-6 in uninfected TG cell cultures was 20.5 +/- 2.3 ng/ml, whereas latently infected TG cells produced significantly less IL-6 (12.1 +/- 1.9 ng/ml). Supernates from TG cell cultures also contained detectable levels of C-10, MCP-1 and eotaxin but little to no MIP-1alpha, MIP-1beta, or MIP-2. While there were no differences in the basal level of MCP-1 and eotaxin in TG cell cultures from HSV-1-infected and uninfected mice, C10 levels were significantly higher in TG cultures originating from infected mice compared to uninfected ones (5.86 +/- 0.61 ng/ml compared to 1.18 +/- 0.16 ng/ml). Hyperthermic stress (43 degrees C, 180 min), which induces reactivation of latent HSV-1 from TG cell cultures, significantly reduced IL-6 and C-10 levels from both uninfected and latently infected TG cell cultures. However, there was no correlation between cytokine/chemokine levels and HSV-1 reactivation. Immunofluorescent studies showed TG cell cultures contained 10% MAC-3+ staining cells (macrophage specific) but no dendritic cells. By comparison, cells from freshly isolated TG contained 6% positive dendritic cells but < 1% MAC-3 + cells. Both in vivo and in vitro TG consisted of a low percentage of CD3+ and CD8+ cells. Hyperthermic stress (43 degrees C for 3 h) eliminated the lymphocyte population as determined by RT-PCR. Whereas no spontaneous reactivation has been reported in mice, spontaneous reactivation occurred in 4.5% (10/220) of TG cell cultures surveyed over a 20 day period. Collectively, the dichotomy between HSV-1 replication and reactivation comparing the in vitro and in vivo HSV-1 latency models may reside, in part, to the differences in the levels of cytokines, chemokines and immune cell populations within the microenvironment of the in vitro and in vivo TG.
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PMID:Cytokine and chemokine production in HSV-1 latently infected trigeminal ganglion cell cultures: effects of hyperthermic stress. 963 Jan 59

Hypersensitivity pneumonitis (HP) is a granulomatous, inflammatory lung disease caused by inhalation of organic Ags, most commonly thermophilic actinomycetes that cause farmer's lung disease. The early response to Ag is an increase in neutrophils in the lung, whereas the late response is a typical Th1-type granulomatous disease. Many patients who develop disease report a recent viral respiratory infection. These studies were undertaken to determine whether viruses can augment the inflammatory responses in HP. C57BL/6 mice were exposed to the thermophilic bacteria Saccharopolyspora rectivirgula (SR) for 3 consecutive days per wk for 3 wk. Some mice were exposed to SR at 2 wk after infection with respiratory syncytial virus (RSV), whereas others were exposed to SR after exposure to saline alone or to heat-inactivated RSV. SR-treated mice developed a typical, early neutrophil response and a late granulomatous inflammatory response. Up-regulation of IFN-gamma and IL-2 gene expression was also found during the late response. These responses were augmented by recent RSV infection but not by heat-inactivated RSV. Mice with a previous RSV infection also had a greater early neutrophil response to SR, with increased macrophage inflammatory protein-2 (MIP-2, murine equivalent of IL-8) release in bronchoalveolar lavage fluid. These studies suggest that viral infection can augment both the early and late inflammatory responses in HP.
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PMID:Viral infection modulates expression of hypersensitivity pneumonitis. 1035 92

After primary immunization with myelin/oligodendrocyte glycoprotein, CD28(-/-) mice developed experimental autoimmune meningitis (EAM) rather than experimental autoimmune encephalomyelitis (EAE). Cytokine and chemokine production in EAE and EAM were compared to understand the differences in disease phenotype. T cells from the central nervous system lesions of mice with either EAE or EAM expressed intracellular TNF-alpha. Splenic T cells from mice with EAM produced TNF-alpha and IL-6 but no IL-2. Conversely, EAE-derived splenic T cells produced TNF-alpha and IL-2 but no IL-6. Altered T cell differentiation in EAM was not due to a Th1 to Th2 shift, because equivalent amounts of T cell IFN-gamma mRNA were produced in both diseases. Neutrophils also produced inflammatory mediators such as TNF-alpha and IL-6 in EAM. Autocrine production of MIP-2 mRNA was observed in neutrophils from mice with EAM but not EAE. Therefore, distinct patterns of cytokines and chemokines distinguish EAE and EAM.
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PMID:Differential cytokine and chemokine production characterizes experimental autoimmune meningitis and experimental autoimmune encephalomyelitis. 1063 96

Natural killer (NK) cells play an important role in innate and adaptive immune responses to obligate intracellular pathogens. Nevertheless, the regulation of NK cell trafficking and migration to inflammatory sites is poorly understood. Exodus-1/MIP-3alpha/LARC, Exodus-2/6Ckine/SLC, and Exodus-3/MIP-3beta/ELC/CKbeta-11 are CC chemokines that share a unique aspartate-cysteine-cysteine-leucine motif near their amino terminus and preferentially stimulate the migration of T lymphocytes. The effects of Exodus chemokines on human NK cells were examined. Exodus-1, -2, and -3 did not induce detectable chemotaxis of resting peripheral blood NK cells. In contrast, Exodus-2 and -3 stimulated migration of polyclonal activated peripheral blood NK cells in a dose-dependent fashion. Exodus-2 and -3 also induced dose-dependent chemotaxis of NKL, an IL-2-dependent human NK cell line. Results of modified checkerboard assays indicate that migration of NKL cells in response to Exodus-2 and -3 represents true chemotaxis and not simply chemokinesis. Exodus-1, -2, and -3 did not induce NK cell proliferation in the absence of other stimuli. Nevertheless, Exodus-2 and -3 significantly augmented IL-2-induced proliferation of normal human CD56(dim) NK cells. In contrast, Exodus-1, -2, and -3 did not affect the cytolytic activity of resting or activated peripheral blood NK cells. Expression of message for CCR7, a shared receptor for Exodus-2 and -3, was detected in activated polyclonal NK cells and NKL cells but not resting NK cells. Taken together, these results indicate that Exodus-2 and -3 can participate in the recruitment and proliferation of activated NK cells. Exodus-2 and -3 may regulate interactions between T cells and NK cells that are crucial for the generation of optimal immune responses.
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PMID:Regulation of human natural killer cell migration and proliferation by the exodus subfamily of CC chemokines. 1067 70

An external evaluation program for measuring the performance of laboratories testing for cytokines and immune activation markers in biological fluids was developed. Cytokines, chemokines, soluble cytokine receptors, and other soluble markers of immune activation (CSM) were measured in plasma from a healthy human immunodeficiency virus (HIV)-seronegative reference population and from HIV-seropositive individuals as well as in supernatant fluids from in vitro-stimulated human immune cells. The 14 components measured were tumor necrosis factor (TNF) alpha, gamma interferon, interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-10, Rantes, MIP-Ia, MIP-Ibeta, soluble TNF receptor II, soluble IL-2 receptor alpha, beta(2)-microglobulin, and neopterin. Twelve laboratories associated with the Adult and Pediatric AIDS Clinical Trial Groups participated in the study. The performance features that were evaluated included intralaboratory variability, interlaboratory variability, comparison of reagent sources, and ability to detect CSM in the plasma of normal subjects as well as the changes occurring in disease. The principal findings were as follows: (i) on initial testing, i.e., before participating in the program, laboratories frequently differed markedly in their analytic results; (ii) the quality of testing of a CSM in individual participating laboratories could be assessed; (iii) most commercial kits allowed distinction between normal and abnormal plasma CSM levels and between supernatants of stimulated and unstimulated cells; (iv) different sources of reagents and reference standards frequently provided different absolute values; (v) inexperienced laboratories can benefit from participating in the program; (vi) laboratory performance improved during active participation in the program; and (vii) comparability between analyses conducted at different sites can be ensured by an external proficiency testing program.
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PMID:Need for an external proficiency testing program for cytokines, chemokines, and plasma markers of immune activation. 1088 48

The discovery that inoculation of DNA leads to strong and long lasting immune responses generated enthusiasm to assess the efficacy of various genetically engineered vaccines against mucosally acquired infections. Various techniques have been used to generate the most suitable DNA vaccines, ranging from immunization with naked DNA to utilizing genetically engineered recombinant viruses and bacteria to deliver the DNA. Different DNA vaccine modalities and mucosal immune responses to them have been discussed. It has been shown that even though intramuscular and intradermal immunization with these vaccines generates strong systemic responses, mucosal responses are not induced. It has been proposed that the site of immunization determines mucosal immune responses and that primed lymphocytes preferentially accumulate at sites where they have been induced thus generating the strongest cellular and antibody responses at the site of vaccination. The impact of the site of induction on mucosal immune responses to vaccines is discussed. It is possible to enhance desired vaccine effects in the mucosa and to modify the undesirable side effects. Cytokines such as IL-2, IL-12, IL-15 and IL-18 have been used to enhance CTL activity while IL-5, IL-6 and the chemokine MIP-1 alpha have shown the capacity to increase IgA responses to vaccines.
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PMID:Targeting the mucosa: genetically engineered vaccines and mucosal immune responses. 1119 91

We describe the genomic organization of a recently identified CC chemokine, MIP3alpha/CCL20 (HGMW-approved symbol SCYA20). The MIP-3alpha/CCL20 gene was cloned and sequenced, revealing a four exon, three intron structure, and was localized by FISH analysis to 2q35-q36. Two distinct cDNAs were identified, encoding two forms of MIP-3alpha/CCL20, Ala MIP-3alpha/CCL20 and Ser MIP-3alpha/CCL20, that differ by one amino acid at the predicted signal peptide cleavage site. Examination of the sequence around the boundary of intron 1 and exon 2 showed that use of alternative splice acceptor sites could give rise to Ala MIP-3alpha/CCL20 or Ser MIP-3alpha/CCL20. Both forms of MIP-3alpha/CCL20 were chemically synthesized and tested for biological activity. Both flu antigen plus IL-2-activated CD4(+) and CD8(+) T lymphoblasts and cord blood-derived dendritic cells responded to Ser and Ala MIP-3alpha/CCL20. T lymphocytes exposed only to IL-2 responded inconsistently, while no response was detected in naive T lymphocytes, monocytes, or neutrophils. The biological activity of Ser MIP-3alpha/CCL20 and Ala MIP-3alpha/CCL20 and the tissue-specific preference of different splice acceptor sites are not yet known.
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PMID:Genomic organization of the CC chemokine mip-3alpha/CCL20/larc/exodus/SCYA20, showing gene structure, splice variants, and chromosome localization. 1135 63

Despite increasing evidence for the role of the chemokine system in leukocyte trafficking, the mechanism underlying the induction of chemokine receptors is poorly understood. Here, we investigated how CCR5, a chemokine receptor implicated in T cell migration to inflammatory sites, is induced in the T cell. CCR5 mRNA was hardly detected in resting T cells and marginally induced following T cell receptor (TCR) stimulation. However, TCR-triggered T cells expressed IL-12 receptor, and stimulation with recombinant IL-12 resulted in high levels of CCR5 expression on both CD4(+) and CD8(+) T cells. In contrast, IL-2 failed to up-regulate CCR5 expression. The effect of IL-12 was selective to CCR5 because IL-12 did not up-regulate CXCR3 expression. Surface expression of CCR5 was shown by staining with anti-CCR5 monoclonal antibody. Stimulation of these CCR5-positive T cells with the relevant chemokine MIP-1 alpha elicited Ca(2+) influx, showing that IL-12-induced CCR5 is functional. These results indicate a critical role for IL-12 in the induction of CCR5 on TCR-triggered T cells.
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PMID:A critical role for IL-12 in CCR5 induction on T cell receptor-triggered mouse CD4(+) and CD8(+) T cells. 1150 Aug 25

Cytokines and beta-chemokines are important mediators of the immune system and are expressed in many infectious diseases. To study cytokine and beta-chemokine profiles during pathogenesis of lentiviral infection and progression to AIDS in rhesus macaques, we established new quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays based on TaqMan chemistry. Using synthetic RNA standards, we quantified mRNAs of IL-2, IL-4, IL-6, IL-10, IL-12 p40, interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), RANTES, macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta in unstimulated peripheral blood mononuclear cells (PBMCs) and lymph nodes from macaques chronically infected with SIV or SHIV. Viremic monkeys with decreased CD4(+) T cell counts (<500 cells/microl) had significantly higher IL-10 mRNA expression than uninfected controls, which parallels the findings in HIV-1-infected humans. In addition, MIP-1 alpha, MIP-1 beta, and RANTES mRNA expression increased in viremic monkeys with decreased CD4(+) T cell counts; gene expression was inversely correlated with CD4(+) T cell counts, but not viral load. The newly established quantitative real-time RT-PCR assays will allow the determination of cytokine and beta-chemokine patterns in rhesus macaques in studies of microbial pathogenesis or vaccine development.
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PMID:Quantitation of simian cytokine and beta-chemokine mRNAs, using real-time reverse transcriptase-polymerase chain reaction: variations in expression during chronic primate lentivirus infection. 1207 58

Proper antigen presentation is paramount to the induction of effective and persistent antitumor immune responses. In a murine model of hepatic metastasis of colon cancer, we found that the numbers of in situ mature dendritic cells (DCs) and macrophages in tumor-infiltrating leukocytes (TILs) were significantly increased in mice treated with the combination therapy of herpes simplex virus thymidine kinase, interleukin 2, and GM-CSF genes when compared with control groups without GM-CSF treatment. Significantly higher levels of IFN-gamma, MIP-1 alpha, mIL-12, and GM-CSF were detected in the tumor after the combination therapy. T cells isolated from the combination therapy-treated mice exhibited higher ex vivo direct CTL activity than those from other treatment groups. Antigen-presenting cells (APCs) enriched from the TILs and liver of the combination therapy-treated mice induced higher levels of proliferation by the splenocytes from long-term surviving mice that had been cured of tumors at early time points (days 4 and 7) whereas significant APC activity was only observed in the spleen at the latter time point (day 7, 14) after the combination therapy. In contrast, APCs isolated from tk or tk + IL-2-treated mice did not induce any significant proliferation. Subcutaneous injection of fluorescence-labeled latex microspheres followed by the combination therapy showed a similar sequential trafficking of microspheres, day 4 after the combination therapy to tumor and day 14 to spleen. The results suggest that APCs recruited by intratumoral gene delivery of GM-CSF can capture antigens, mature to a stage suitable for antigen presentation, and subsequently migrate to the spleen where they can efficiently stimulate antigen-specific T cells.
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PMID:In situ recruitment of antigen-presenting cells by intratumoral GM-CSF gene delivery. 1295 80


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