Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the normal brain, low levels of cytokines are observed, whereas inflammatory disorders of the central nervous system are characterized by an up-regulation of cytokine production. The cellular sources for cytokines in the central nervous system are largely undefined. In the present study, we have analyzed intracerebral cytokine production in normal and Toxoplasma gondii-infected mice using immunohistochemistry, in situ hybridization, flow cytometry of brain-derived leukocytes, and reverse transcriptase polymerase chain reaction detection in various subpopulations of inflammatory cells. In the normal brain, neurons and choroid plexus epithelia expressed interleukin (IL)-1 beta and IL-10. Microglia/macrophages produced IL-1 beta, IL-10, and tumor necrosis factor-alpha In Toxoplasma encephalitis, these cell types exhibited increased levels of the respective cytokines. In addition, microglia/macrophages showed a de novo expression of inducible nitric oxide synthase. CD4+ and CD8+ T cells, which were recruited to the brain, produced IL-2, IL-10, tumor necrosis factor-alpha, and interferon-gamma. IL-4 was exclusively detectable in CD4+ T cells, whereas CD8+ T cells showed expression of IL-1 beta. As chronic Toxoplasma encephalitis was not associated with neuronal degeneration and an up-regulation of neurotrophic factors, some cytokines may also exert neurotrophic and/or neuroprotective properties.
...
PMID:Expression pattern and cellular origin of cytokines in the normal and Toxoplasma gondii-infected murine brain. 906 Aug 39

In vitro, expression of E-selectin is largely restricted to endothelial cells activated by inflammatory cytokines. Under activated conditions, cytokines such as interleukin (IL) 10, released by keratinocytes in large quantities, may also increase the expression of E-selectin on the dermal microvasculature. The aim of the present study was to investigate the expression of E-selectin on cultured human dermal microvascular endothelial cells (HDMEC) isolated from neonatal foreskins when exposed to IL-10. Expression of E-selectin was determined by immunofluorescence microscopy, FACS analysis, an HL-60 cell-binding assay, and quantitative polymerase chain reaction (PCR) analysis. For comparison with large blood vessel cells, the expression of E-selectin on human umbilical vein endothelial cells (HUVEC) was also determined in parallel by FACS and reverse transcriptase-PCR analysis under identical conditions. These studies demonstrate that IL-10 induces the expression of E-selectin on both HDMEC and HUVEC and that the level of expression of HDMEC is comparable with that induced by IL-1 beta and tumor necrosis factor-alpha. When HL-60 cells are incubated with HDMEC pretreated with IL-10, a consistent increase in adherence of HL-60 to endothelial cells is observed. This adherence was found to be mediated by L-selectin. PCR analysis and the quantification of E-selectin cDNA by a novel, highly sensitive and specific PCR-immunoassay demonstrate the induction of E-selectin mRNA at the transcriptional level. The induction of the expression of E-selectin by IL-10 on HDMEC may provide additional insights into the pathogenic mechanism of neutrophil accumulation at the site of inflammation in inflammatory skin diseases.
...
PMID:Interleukin-10 induces E-selectin on small and large blood vessel endothelial cells. 906 42

Tumor regression in experimental systems has been linked to the activities of Th1 cells. It is, therefore, conceivable that Th2 cells interrupt the expression of tumor immunity since interleukin-4 (IL-4) and IL-10 inhibit the generation of Th1 from precursors and modulate the competence of antigen-presenting cells to activate this lymphocyte subpopulation. Naive murine renal cell carcinoma (renca) cells (1 x 10(5)) were implanted into the subcapsule of the left kidney of Balb/c and Balb/c nude mice at 6-8 weeks of age. After 14 days, Th2 cytokine (IL-4 and IL-10) mRNAs as well as transforming growth factor beta1 mRNA, assessed by reverse transcriptase/polymerase chain reaction were upregulated in the spleen of hosts upon naive renca tumor acceptance, while Th1 cytokine (IL-2 and interferon gamma) mRNAs were almost undetectable. In the renca tumor, IL-10 mRNA was detected but IL-2, interferon gamma, and IL-4 were not. Intraperitoneal administration of anti-(mouse IL-4) mAb (11B11) reduced the renca tumor size (P = 0.018) and prolonged host survival (P = 0.03), but did not reduce the acceptance rate of the tumor (P = 0.18). However, prior depletion of CD4+ or CD8+ cells with monoclonal antibodies abrogated the antitumor effects of anti-IL-4 mAb. In addition, the significant antitumor effect of anti-IL-4 mAb was not observed in Balb/c nude hosts. Renca cells were transfected with the mammalian expression vector pCAGGS containing murine IL-4 cDNA or vector alone, then stable IL-4 transfectants (RencaL or RencaH, low- or high-IL-4-producing respectively) and control renca cells (RencaC) were obtained. RencaL cells, RencaH cells, or RencaC cells (1 x 10(5) each) were implanted into the subcapsule of the left kidney of Balb/c, Balb/c nude, and allogenic C3H/HeJ mice, then tumor formation was evaluated 14 days later. When RencaH cells were innoculated into syngeneic Balb/c hosts, tumor volume was marginally suppressed (P = 0.03) and tumors tended to be rejected (P = 0.06) compared with RencaC cells. However, those effects were not observed in Balb/c nude mice. RencaC, RencaL, and RencaH cells were not accepted by allogeneic C3H mice with or without FK506 administration or donor-specific transfusion. The administration of anti-(mouse IL-4) mAb to Balb/c mice significantly suppressed renca tumor growth by a CD4+ and CD8+ T-cell-dependent mechanism. By contrast, relatively high levels of IL-4 production by renca cells and T cells seemed to be required to induce the rejection and growth suppression of IL-4-producing renca cells in syngeneic hosts.
...
PMID:Th2-like response and antitumor effect of anti-interleukin-4 mAb in mice bearing renal cell carcinoma. 906 10

IL-1beta, IL-6, IL-8 and TNF-alpha production by PMNL from 21 HIV-infected (HIV+), including 11 full-blown AIDS, and 20 HIV-uninfected (HIV-) subjects (matched for age and sex to HIV+ ones) was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and ELISA. PMNL from both categories of subjects were strongly stimulated in their actual cytokine production by a mannoprotein fraction (MP-F2) of Candida albicans, as well as by the bacterial lipopolysaccharide (LPS). These stimulatory effects were apparently due to increased cytokine gene expression and were substantially reversed by the physiological inhibitor IL-10. However, PMNL from HIV+ subjects showed increased IL-6 and TNF-alpha gene expression and produced more IL-6 and TNF-alpha than PMNL from HIV- controls, under similar stimulation conditions. This difference could not be attributed to a given stage of HIV infection, any associated medication, or to a generalized increase of gene expression, as quantitatively similar beta-actin and IL-1beta transcripts were detected. Moreover, no significant difference in IL-8 production by the PMNL from HIV+ and HIV- subjects was observed. Our studies suggest that PMNL from HIV+ subjects might add to other cellular sources of IL-6 and TNF-alpha (e.g. monocytes-macrophages) in contributing to the cytokine-dysregulated pattern typical of the HIV+ patient.
...
PMID:Responsiveness of human polymorphonuclear cells (PMNL) to stimulation by a mannoprotein fraction (MP-F2) of Candida albicans; enhanced production of IL-6 and tumour necrosis factor-alpha (TNF-alpha) by MP-F2-stimulated PMNL from HIV-infected subjects. 906 16

To understand the molecular basis of parasite-specific anergy in human lymphatic filariasis caused by the nematode Wuchereria bancrofti, parasite antigen-dependent cellular proliferation and cytokine gene expression were investigated. By reverse transcriptase polymerase chain reaction (RT-PCR), the levels of cytokine mRNA were determined in the peripheral blood mononuclear cells (PBMCs) of different clinical groups of filariasis patients. This includes individuals with circulating microfilariae (MF), patients with chronic lymphatic obstruction (CP), and exposed but uninfected individuals (EN). Those with CP exhibited both a Th2 and a Th1 parasite antigen-driven response. In PBMCs from those with MF, there was a marked downregulation of cellular response to parasite antigens, with lowered expression of Th1-specific cytokines (IFN-gamma and IL-2) and this was paralleled by increased IL-10 expression. The EN individuals had a purely Th1-type pattern with absence of IL-4 and IL-5 expression. Further, the mRNA expression of the costimulatory surface marker, CD80 (B7-1), was not associated with either disease status or IL-10 expression. There was a significant negative correlation between IL-10 mRNA expression and PBMC proliferation in the MF individuals, thus indicating the possible role of IL-10 in antigen-specific hyporesponsiveness.
...
PMID:Elevated IL-10 mRNA expression and downregulation of Th1-type cytokines in microfilaraemic individuals with Wuchereria bancrofti infection. 907 9

An accumulation of elevated numbers of macrophages (M phi) and Ig producing cells is associated with localized and chronically inflamed gingiva of patients with adult periodontitis. When gingival lymphocytes were isolated from inflamed tissues and examined by flow cytometry, approximately 20-30% of lymphocytes were CD4+ T cells. For the analysis of Th1 and Th2 cytokine expression by these CD4+ T cells, RNA was extracted and reverse transcriptase polymerase chain reaction (RT-PCR) was performed by using specific 5' and 3' primers for IFN-gamma and IL-2 (Th1), IL-4, IL-5, IL-6, IL-10 and IL-13, (Th2) and beta-actin (housekeeping gene). Two distinct cytokine profiles were noted based on the expression of selected Th1 and Th2 cytokines. Thus, one pattern was represented by the expression of mRNA for IFN-gamma, IL-6, IL-10 and IL-13, while the other case consisted of mRNA for IFN-gamma, IL-6, and IL-13. Except for a few cases, messages for IL-2, IL-4 and IL-5 were not detected by cytokine-specific RT-PCR. The predominant expression of Th2 cytokines (e.g. IL-6, IL-10 and IL-13) may contribute to the induction of high B cell responses in local disease sites. On the other hand, lack of IL-4 may be responsible for the accumulation of M phi in diseased periodontium. We also investigated whether a relationship exists between IL-4 receptor (IL-4R) expression and M phi persistence in the absence of exogenous IL-4. Gingival M phi, when compared with monocytes (MN)/M phi from peripheral blood mononuclear cells (PBMC), expressed high levels of IL-4R mRNA. When gingival M phi were incubated with recombinant IL-4 (rIL-4), the cell viability was dramatically reduced by apoptosis. These findings clearly show that the lack of IL-4 may contribute to the persistent occurrence of M phi at the disease site and addition of exogenous rIL-4 to gingival M phi cultures leads to cell death by apoptosis.
...
PMID:Molecular and cellular mechanisms for periodontal diseases: role of Th1 and Th2 type cytokines in induction of mucosal inflammation. 908 20

In the present study we investigated cytokine mRNA expression by peripheral blood mononuclear cells (PBMC) from patients with cystic echinococcosis (CE) after stimulation with different antigens. By using reverse transcriptase polymerase chain reaction (RT-PCR) we could demonstrate that restimulation with crude Echinococcus granulosus antigen (Eg-Ag) induced or enhanced Th2 cytokine mRNA expression, especially IL-5 (by using antigen from sheep cyst fluid) in 23 out of 26 investigated CE patients and IL-10 (by using antigen from camel cyst fluid) in 10 out of 10 investigated CE patients. In contrast, IL-5 mRNA expression was absent in PBMC of healthy controls after Eg-Ag stimulation. To determine the specificity of this reaction we stimulated PBMC from 11 CE patients with crude Echinococcus multilocularis antigen (Em-Ag) and PBMC from 8 CE patients with Toxocara canis antigen (Tc-Ag). We found that the PBMC of patients showed a similar mRNA cytokine pattern on stimulation with Em-Ag when compared with Eg-Ag stimulation. The cytokine mRNA pattern on stimulation with Tc-Ag, however, resembled the cytokine mRNA pattern of unstimulated PBMC. Furthermore, the stimulation of PBMC with crude Mycobacterium tuberculosis antigen (H37Ra) and purified protein derivative (PPD) of M. tuberculosis revealed distinct IL-5 mRNA expression in all investigated CE patients, whereas in healthy controls IL-5 mRNA expression was very weak or totally absent. Thus, our results indicate an induction of Th2 cytokine mRNA expression in CE patients, which is frequently observed in parasite infections. Interestingly, this response persists after stimulation with tuberculosis antigens, which normally induce Th1 response.
...
PMID:T-lymphocyte cytokine mRNA expression in cystic echinococcosis. 909 87

The in vitro mixed lymphocyte reaction (MLR) is a useful model to study alloresponsiveness to histocompatibility antigens. Secretion of different cytokine proteins in the supernatant of allo-MLR cultures has been reported in a few studies with no reference to results in auto-MLR. Since most cytokines are autocrine factors, their levels in the supernatant may not reflect the actual intracellular production. Therefore, we studied cytokine gene expression in auto- and allo-MLR by Northern dot blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. mRNA for IL-beta and IL-8 was detected in both auto- and allo-MLR by Northern dot blotting. mRNA for IL-2, gamma-IFN, TNF-alpha, IL-4, IL-10 and IL-2 receptor (IL-2R) was not found by Northern dot blotting and could only be detected by RT-PCR. Expression of mRNA for IL-4, IL-10, TNF-alpha, gamma-IFN and IL-2R by RT-PCR analysis was seen in both auto- and allo-MLR. There was slightly increased expression of gamma-IFN, IL-2R and TNF-alpha in allo-MLR in comparison to auto-MLR. However, IL-2 was exclusively expressed in allo-MLR and was detected as early as 5 h of initiation of culture. These results indicate that mRNA expression for a number of cytokines can be seen in both auto- and allo-MLR using RT-PCR analysis. However, the consistent expression of IL-2 in the allo-MLR indicates that it is an important cytokine which discriminates an allo- from an autoresponse. These findings suggest that detection of IL-2 gene expression by RT-PCR may be useful for immune monitoring of allograft rejection.
...
PMID:Selective expression of the interleukin-2 gene discriminates between the auto- and allo-mixed lymphocyte reaction. 910 32

The small bowel has a unique amount of closely associated lymphoid tissue in the form of mesenteric lymph nodes (MLNs) and Peyer's patches (PPs). It is rather unclear how this may affect the immune response to transplants involving small bowel. It is clear, however, that host-derived leukocytes infiltrate this lymphoid tissue very rapidly after transplantation of small bowel, which suggests the possibility of an early immune response within this compartment. To investigate this possibility, we analyzed, using a semiquantitative reverse transcriptase-polymerase chain reaction, the level of cytokine transcripts within isolated MLNs and PPs for the first 7 days after small bowel transplantation. Heterotopic small bowel (n=32) transplants were performed using the following rat strain combinations: syngeneic Lewis (Lew)-->Lew (n=8), blood group D Agouti (DA)-->DA (n=8), allogeneic Lew-->DA (n=8), and allogeneic DA-->Lew (n=8). Two rats from each group were killed at 1, 3, 5, and 7 days after transplantation. RNA was prepared separately from PPs and MLNs before analysis of transcripts for interleukin (IL) 2, IL-4, IL-10, IL-6, IL-1alpha, and interferon (IFN) gamma. No increase in transcripts for IL-2 or IL-10 was observed in either PPs or MLNs of syngeneic grafts. A small rise in IL-6, IL-1alpha, and IFN-gamma transcripts was seen in MLNs and IFN-gamma transcripts in PPs of syngeneic grafts. In contrast, in allografts an extremely early increase in cytokine transcripts was observed; all cytokine transcripts tested were elevated within the first 24 hr after transplantation. Indeed, the peak response of both IL-2 and IL-10 occurred within 1 to 3 days after grafting. This early immune response in the lymphoid tissue may not be controlled by immunosuppression delivered only at the time of transplantation, and therefore may be responsible for the difficulty in achieving adequate immunosuppression in small bowel transplantation.
...
PMID:The immune response following small bowel transplantation. II. A very early cytokine response in the gut-associated lymphoid tissue. 913 73

Direct delivery of the herpes simplex virus thymidine kinase (HSVtk) gene, in combination with the prodrug ganciclovir (GC), has been used for the treatment of localised, inoperable tumours. Several groups have shown that when rodent tumours are ablated in vivo with suicide genes, anti-tumour immunity can also be generated. Hence, this approach may also be useful in treating disseminated disease. Here we have studied the mechanisms associated with this anti-tumour immunity. In B16 HSVtk+ tumours being killed in vivo with GC treatment, we observed the induction of a pronounced intratumoural infiltrate of macrophages, CD4+ and CD8+ T cells. In addition, using reverse transcriptase polymerase chain reaction, expression of interleukin (IL)-2, IL-12, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and granulocyte/macrophage colony-stimulating factor (GM-CSF) but not IL-4, IL-6 or IL-10, was observed, a profile of cytokine expression which resembles that of a Th1 immune response. To complement these findings, we also investigated the mechanisms by which expression of HSVtk leads to cell death. Our data show that B16/HSVtk+ cells die predominantly by necrosis, rather than apoptosis, on exposure to GC, a process which may be associated with the generation of anti-tumour inflammatory responses. From these data we propose a model for the induction of anti-tumour immunity using suicide genes and discuss the development of improved vectors for gene therapy to augment these effects in vivo.
...
PMID:Generation of an anti-tumour immune response in a non-immunogenic tumour: HSVtk killing in vivo stimulates a mononuclear cell infiltrate and a Th1-like profile of intratumoural cytokine expression. 913 53


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

---