Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to identify disease-related changes in lymphocyte populations within ileal mucosae of calves with cryptosporidiosis. Groups of five neonatal calves were orally infected at 3 days of age with 10(8) oocysts and maintained in enteric-pathogen-free conditions until clinical disease was established or until the animals had recovered from disease. Age-matched uninfected calves were used for comparison. Ileal mucosal lymphocytes were collected, quantitated, and phenotyped to determine whether changes in lymphocyte composition occurred in infected animals. We observed significantly larger numbers of intraepithelial CD8+ T lymphocytes in ileal mucosae from acutely infected calves compared with those from control animals. In addition, a proportion of intraepithelial CD4+ T cells from acutely infected calves coexpressed CD25, whereas there was an absence of coexpressed CD25 on CD4+ T cells from control calves. Ex vivo reverse transcriptase PCR of RNA from intraepithelial lymphocytes from control calves showed a cytokine expression pattern consisting of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), while intraepithelial lymphocytes from calves with cryptosporidiosis expressed IFN-gamma but not TNF-alpha. Together, the results indicate that changes occur in the ileal intraepithelial lymphocyte population coincidently with Cryptosporidium parvum-induced enteric disease.
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PMID:Activation of intestinal intraepithelial T lymphocytes in calves infected with Cryptosporidium parvum. 897 10

FK-506 (Tacrolimus) has been shown to block T cell proliferation in vitro by inhibiting the generation of several lymphokines, especially interleukin (IL)-2, but little direct evidence is available to support the view that the immunosuppressive effects of FK-506 in vivo are mediated by a similar inhibition of lymphokine cascade. To investigate the mechanisms of FK-506-induced immunosuppression, the effects of FK-506 on cell-mediated immunity to Hymenolepis nana were examined in mice. FK-506 administration into BALB/c mice daily at a dose of 10.0 mg/kg (but not 5.0 mg/kg) for 5 days caused suppression of protective immunity against H. nana challenge infection. During the infection of mice with H. nana, IL-2 and interferon (IFN)-gama were produced by mesenteric lymph node (MLN) cells with a time course corresponding to that of MLN T cell proliferation. These responses were completely suppressed by repeated administration of FK-506 for 5 days at a dose of 10.0 mg/kg/day (but not 5.0 mg/kg/day). In contrast to the effects of FK-506 on IL-2 and IFN-gamma productions in MLN, IL-1 and tumor necrosis factor-alpha in the intestinal wall, which were enhanced by H. nana infection, were not completely decreased as a result of 10.0 mg/kg FK-506 treatment. The reverse transcriptase-PCR revealed complete inhibition of IL-2 and IFN-gamma mRNA expression on mesenteric L3T4+ cells that were induced by H. nana infection, when mice were given 10.0 mg/kg/day FK-506 for 5 days. These results strongly suggest that FK-506 affects cell-mediated immunity in vivo with mechanisms similar to those observed in vitro.
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PMID:Mode of action of FK-506 on protective immunity to Hymenolepis nana in mice. 898 61

For determination of the kinetics of cytokine production and its possible role in host resistance to Angiostrongylus cantonensis in the mouse, Th1 [interleukin 2 (IL-2) and interferon gamma (IFN-gamma] and Th2 (IL-5 and IL-4) cytokine production in the cerebrospinal fluid (CSF), sera, and culture supernatants of spleen cells (SC) or cervical lymph-node cells (CLNC) of infected BALB/c and C57BL/6 mice was assessed by a sandwich enzyme-linked immunosorbent assay (ELISA). IL-5 and IL-4 were detected in CSF of both strains, with a peak response occurring at around days 12-15 and 20 postinfection (p.i.), respectively. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay also revealed prominent IL-5 and IL-4 mRNA expression in T-cells but not in eosinophils in CSF. SC and CLNC stimulated with A. cantonensis young adult-worm antigen released IL-5 in vitro at and after day 20 p.i. Contrarily, IFN-gamma production in CSF and SC or CLNC culture supernatants was almost negligible before day 30 p.i. IL-5, IL-4, and IL-2 production in culture supernatants was rather prominent in resistant C57BL/6 mice as opposed to susceptible BALB/c mice as assessed by the magnitude of increase over preinfection levels. Antigen-specific IgG1 (but not IgG2a) responses were more prominent in C57BL/6 mice than in BALB/c mice. These data suggest that systemic and local Th2 cytokine responses, especially those involving IL-5, are predominant in A. cantonensis-infected mice and that IL-5 is an important cytokine underlying the innate resistance of the mouse against A. cantonensis.
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PMID:Cytokine responses in mice infected with Angiostrongylus cantonensis. 900 Feb 26

In a murine model of rickettsial disease in which, as in human rickettsioses, endothelial cells are the major target of infection, depletion of IFN-gamma or TNF-alpha converts a sublethal infection into a uniformly fatal disease with overwhelming rickettsial growth and decreased nitric oxide (NO) synthesis. The kinetics of NO production and rickettsial survival and growth were examined on Days 1, 2, and 3 after inoculation of endothelial cells with Rickettsia conorii under four different experimental conditions: (a) no cytokine treatment, (b) treatment with IFN-gamma and TNF-alpha, (c) treatment with cytokines and NG monomethyl-L-arginine, a competitive inhibitor of NO synthesis, and (d) treatment with sodium nitroprusside, a source of NO. Endothelial cells were examined for the presence of inducible nitric oxide synthase mRNA by specific reverse transcriptase-PCR after stimulation with IFN-gamma and TNF-alpha. Cytokine-stimulated and unstimulated rickettsiae-infected endothelial cells were examined by electron microscopy to observe the cellular and rickettsial events. Transformed and diploid mouse endothelial cells stimulated by the combination of recombinant murine IFN-gamma and TNF-alpha killed intracellular Rickettsia conorii by a mechanism that required the synthesis of NO. The antirickettsial effect and NO synthesis were inhibited by treatment of endothelial cells with NG monomethyl-L-arginine. Addition of nitroprusside, which released NO, also exerted a strong antirickettsial effect in the absence of IFN-gamma and TNF-alpha. Endothelial inducible nitric oxide synthase mRNA was detected 4 hours after cytokine stimulation, increased substantially at 8 hours, and decreased to low levels by 72 hours. Ultrastructural evaluation revealed that endothelial cells effected rickettsial killing in association with autophagy. Double membranes of endothelial cell granular endoplasmic reticulum surrounded rickettsiae, which were also observed being destroyed within phagolysosomes. This study demonstrated for the first time that endothelial cells are capable of killing rickettsiae. When stimulated by the combination of IFN-gamma and TNF-alpha, mouse endothelial cells kill Rickettsia conorii by an NO-dependent mechanism. Within the endothelium, NO exerts a rickettsicidal effect.
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PMID:Cytokine-induced, nitric oxide-dependent, intracellular antirickettsial activity of mouse endothelial cells. 901 Apr 56

IFN-gamma has a direct antitumor effect on many tumor cell lines mediated through the IFN-gammaR. One effect of IFN-gamma is to induce the nuclear transcription factor IFN regulatory factor-1 (IRF-1), which may function as a tumor suppressor. In this study, mouse IRF-1 cDNA under a high constitutive expression promoter was transfected into the highly aggressive, nonimmunogenic MCA 101 murine sarcoma. Clones were obtained by G418 selection and screened for IRF-1 mRNA expression by reverse transcriptase-PCR (RT-PCR). High expression clones had high levels of two MHC class I proteins (H-2Kb and H-2Db) on the cell surface that correlated with increased levels of class I mRNA by RT-PCR. Furthermore, these clones also had increased levels of MHC class II protein (I-Ab), which correlated with increased levels of one subunit of class II mRNA by RT-PCR. IRF-1-expressing clones had markedly diminished cell growth in vitro and decreased anchorage-independent growth in a soft agar assay. These clones also demonstrated markedly prolonged tumor latency and slowed growth in syngeneic C57BL/6 mice. IRF-1 gene-transfected cells had shortened tumor latency and formed faster growing tumors in gamma-irradiated immunodeficient mice compared with results in immunocompetent mice. Mice immunized with IRF-1-transfected cells were protected against subsequent challenge with IRF-1 transfected cells and also demonstrated greater tumor latency and slower tumor growth against subsequent challenge with untransfected cells compared with mice immunized with empty vector-transfected cells. These studies demonstrate a tumor suppressor effect of IRF-1, which acts in vivo through both partial reversion of the malignant phenotype and enhanced immune recognition and may play a role in the antitumor effects of IFN-gamma.
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PMID:IFN regulatory factor-1 gene transfer into an aggressive, nonimmunogenic sarcoma suppresses the malignant phenotype and enhances immunogenicity in syngeneic mice. 901 71

Recruitment of lymphocytes is a prominent feature of allergic inflammation. However, the mechanisms by which lymphocytes are attracted to such sites are not understood. Recently, cDNAs encoding a lymphocyte-specific chemokine, lymphotactin (Ltn), were isolated from mouse pro-T cell and human CD8+ T cell libraries, leading us to hypothesize that mast cells might also produce Ltn. Using the reverse transcriptase-PCR and Northern blot analysis, we found that the Ltn gene is inducible in C1.MC/C57.1 and murine bone marrow-cultured mast cells (BMCMC) by Fc(epsilon)RI aggregation. Activation of a human mast cell (HMC-1) or basophil cell line (KU812) similarly led to transcription of Ltn. Fc(epsilon)RI aggregation-dependent Ltn mRNA expression was detected by 1 to 2 h, maximal at 6 h, independent of de novo protein synthesis, and was inhibited by cyclosporin A and dexamethasone. Compared with macrophage inflammatory protein alpha (MIP-1alpha), Fc(epsilon)RI-dependent Ltn and MIP-1alpha mRNA levels were up-regulated by IL-4, but not IFN-gamma, although higher levels of IL-4 (100 and 1000 U/ml) inhibited Ltn expression only; and TGF-beta preferentially enhanced Fc(epsilon)RI-dependent Ltn mRNA levels, suggesting that Ltn and MIP-1alpha have shared and unique regulatory mechanisms. A rabbit polyclonal Ab against a synthetic peptide was developed for use in immunoblot analysis and detected a 15-kDa Ltn protein within mast cell pellets and in the supernatants of mast cells following Fc(epsilon)RI aggregation. Ltn is thus expressed in mast cells and may contribute to the recruitment of lymphocytes to areas of allergic inflammation.
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PMID:Lymphotactin gene expression in mast cells following Fc(epsilon) receptor I aggregation: modulation by TGF-beta, IL-4, dexamethasone, and cyclosporin A. 901 79

Stimulation of a cultured human salivary gland (HSG) cell line by interferon (IFN)-gamma leads to HLA-DR gene expression concomitant with inflammatory cytokine genes such as IL-1 beta, tumor necrosis factor (TNF)-alpha, and IL-6 in vitro. IFN-gamma-induced HLA-DR mRNA expression was clearly detected at 2 h after the stimulation, and thereafter its level of gene expression increased until day 7 on HSG cells by reverse transcriptase (RT)-PCR. Immunofluorescence analysis revealed that cytoplasmic HLA-DR immunoreactivity was detected for the first time at 2 days after the stimulation, and its immunoreactivity increased gradually until day 7, while no immunoreactivity with HLA-DP and HLA-DQ was observed at any of the days. In addition, the expression of IL-1 beta, TNF-alpha, and IL-6 on the IFN-gamma-stimulated HSG cells was detected by immunohistochemistry and RT-PCR analysis. These results indicate that human salivary gland cells can be induced to express HLA-DR mRNA by IFN-gamma concomitant with inflammatory cytokine gene expressions such as IL-1 beta, TNF-alpha, and IL-6.
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PMID:Expression of HLA-DR and cytokine genes on interferon-gamma-stimulated human salivary gland cell line. 906 8

Certain diets can have major effects on the development of IDDM in DP-BB rats, but data are scant on the timing, dose, and mechanisms involved. We therefore determined the dose response, timing, and duration of exposure required to induce diabetes, and characterized the effects of nutritionally adequate diets with widely different diabetogenicity on the pancreatic islet area and cytokines. DP-BB rats were fed a diabetogenic, cereal-based, NIH-07 (NIH) diet or a protective, casein or hydrolyzed casein (HC)-based, semipurified diet. Rats were fed from weaning to 50 or 100 days with the HC diet and then switched to the NIH diet, or fed the NIH diet from weaning to 50 days and switched to the HC diet. Pancreas histology and diabetes outcome were determined. Semiquantitative morphometric analyses of hematoxylin and eosin-stained sections of pancreas from 41-day-old rats were also carried out. Diet-induced effects on pancreatic cytokine levels were measured at 70 days using reverse transcriptase-polymerase chain reaction analysis of gamma-interferon (IFN-gamma), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta). Long-term daily exposure, particularly around the beginning of puberty to late adolescence (50-100 days), was important for development of diabetes. DP-BB rats could be rescued from diabetes development by feeding them a low-diabetogen HC diet as late as 50 days. Diabetes frequency was highest in rats fed 70% and 100% NIH diets. By age 41 days, before classic insulitis, the islet area in HC-fed DP-BB rats was 65% greater than in NIH-fed rats. By 70 days, when mononuclear cells were visible in the islets of most NIH-fed, but not HC-fed rats, the more pronounced inflammatory process in NIH-fed rats was associated with a Th1 cytokine pattern (high IFN-gamma and low IL-10 and TGF-beta), whereas the pancreases of HC-fed rats showed fewer infiltrating cells, low levels of IFN-gamma, and high levels of TGF-beta, typical of a Th2 cytokine pattern. Thus dietary modification can occur as late as puberty. Further, long-term exposure to sufficient amounts of food diabetogens between 50 and 100 days was required for maximum diabetes induction. The islet area was modified by diet before signs of classic insulitis. Pancreatic inflammation in NIH-fed animals is a Th1-dependent phenomenon. The HC diet inhibited insulitis and was associated with a Th2 cytokine pattern in the pancreas, protecting diabetes-prone rats from developing diabetes.
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PMID:Potential mechanisms by which certain foods promote or inhibit the development of spontaneous diabetes in BB rats: dose, timing, early effect on islet area, and switch in infiltrate from Th1 to Th2 cells. 907 98

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.
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PMID:Elevated IL-10 mRNA expression and downregulation of Th1-type cytokines in microfilaraemic individuals with Wuchereria bancrofti infection. 907 9

Nonspecific cross-reacting antigen (NCA), a member of the carcinoembryonic antigen (CEA) family, shows increased expression levels in colorectal cancer tissues. To elucidate the mechanism, we observed the effect of interferon (IFN)-gamma on the expression level of NCA mRNA in colon cancer cell lines by quantitative reverse transcriptase-polymerase chain reaction assay. IFN-gamma induced NCA mRNA in three of four cell lines tested. The effect of anti-fibronectin receptor (FnR) antibody on the expression of NCA mRNA was then examined in the same manner. Colo201 and DLD-1 cells showed an increased expression level of NCA mRNA after stimulation with the antibody. On flow cytometry, FnR was expressed in only two, Colo201 and DLD-1, of the five cell lines tested. These findings indicate that IFN-gamma and anti-FnR antibody induce NCA mRNA in cultured colon cancer cell lines, suggesting that inflammatory response and cell-to-extracellular matrix interaction may be related to the increased expression of NCA mRNA in colorectal cancers in vivo.
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PMID:Induction of nonspecific cross-reacting antigen mRNA by interferon-gamma and anti-fibronectin receptor antibody in colon cancer cells. 908 68


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