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

The effects of staphylococcal enterotoxin B (SEB), a Staphylococcus aureus-derived bacterial superantigen, on expression of intercellular adhesion molecule-1 (ICAM-1) were examined in cultured normal and transformed (DJM-1 cells) human keratinocytes by flow cytometry, confocal microscopy, digital image processing, and reverse transcriptase-polymerase chain reaction. SEB significantly upregulated ICAM-1 expression in the interferon-gamma (IFN-gamma)-pretreated, HLA-DR-positive normal keratinocytes and DJM-1 cells in a dose-dependent manner, but not in the untreated, HLA-DR-negative cells. Other toxins such as diphtheria and pertussis toxins did not have the effect. The distribution of SEB and HLA-DR molecules was identical on the IFN-gamma-treated, HLA-DR-positive DJM-1 cells by confocal microscopy. Digital image processing analysis demonstrated that SEB induced a transient increase of intracellular calcium concentration only in the IFN-gamma-treated DJM-1 cells. Pretreatment of the IFN-gamma-treated DJM-1 cells with anti-major histocompatibility complex class II monoclonal antibody completely blocked the effect of SEB. Furthermore, ICAM-1 mRNA was detected in the IFN-gamma-pretreated, SEB-exposed normal keratinocytes by reverse transcriptase-polymerase chain reaction. Our results demonstrate that SEB binds to keratinocytes, presumably via major histocompatibility complex class II molecules such as HLA-DR, triggers calcium mobilization, and induces the synthesis of ICAM-1 molecules. We speculate that, in various cutaneous disorders, SEB penetrates the epidermis and interacts with HLA-DR-positive keratinocytes to upregulate ICAM-1 expression, thus modulating the course of the inflammatory process.
 ...
PMID:Staphylococcal enterotoxin B upregulates expression of ICAM-1 molecules on IFN-gamma-treated keratinocytes and keratinocyte cell lines. 756 Nov 55

An infectious molecular clone of human T-cell leukemia virus type I (HTLV-I) was derived from an HTLV-I-transformed rabbit T-cell line, RH/K30, obtained by coculture of rabbit peripheral blood mononuclear cells (PBMC) with the human HTLV-I-transformed cell line MT-2. The RH/K30 cell line contained two integrated proviruses, an intact HTLV-I genome and an apparently defective provirus with an in-frame stop codon in the env gene. A genomic DNA fragment containing the intact HTLV-I provirus was cloned into bacteriophage lambda (K30 phi) and subcloned into a plasmid vector (K30p). HTLV-I p24gag protein was detected in culture supernatants of human and rabbit T-cell and fibroblast lines transfected with these clones, at levels comparable to those of the parental cell line RH/K30. Persistent expression of virus was observed in one of these lines, RL-5/K30p, for more than 24 months. Biologic characterization of this cell line revealed the presence of integrated HTLV-I provirus, spliced and unspliced mRNA transcripts, and typical extracellular type C retrovirus particles. As expected, these virus particles contained HTLV-I RNA and reverse transcriptase activity. The transfected cells also expressed surface major histocompatibility complex class II, whereas no expression of this molecule was detected in the parental RL-5 cell line. Virus was passaged by cocultivation of irradiated RL-5/K30p cells with either rabbit PBMC or human cord blood mononuclear cells, demonstrating in vitro infectivity. The virus produced in these cells was also infectious in vivo, since rabbits injected with RL-5/K30p cells became productively infected, as evidenced by seroconversion, amplification of HTLV-I-specific sequences by PCR from PBMC DNA, and virus isolation from PBMC. Availability of infectious molecular clones will facilitate functional studies of HTLV-I genes and gene products.
 ...
PMID:Characterization of an infectious molecular clone of human T-cell leukemia virus type I. 788 47

We have recently demonstrated that rat cytomegalovirus (RCMV) infection induces an early inflammatory response in the adventitia (perivasculitis) and in the subendothelial space (endothelialitis) as well as doubles smooth muscle cell (SMC) proliferation and intimal thickening of rat aortic allografts performed from the DA (AG-B4, RT1a) to the WF (AG-B2, RT1v) strain. In this study, the impact of RCMV infection on the structure of inflammation in the allograft adventitia and on the expression of SMC growth factors in the allograft vascular wall was investigated. The recipient rats were inoculated with 10(5) plaque-forming U of RCMV Maastricht strain or left noninfected and used as controls. The allografts were removed at 7 days and 1 and 3 months after transplantation and processed for morphometry and immunohistochemistry. RNA was isolated for reverse transcriptase polymerase chain reaction (RT-PCR). RCMV infection was associated with significantly upregulated presence (P < .05) of T helper (W3/25), T cytotoxic (OX8), and natural killer (3.2.3) cells in the allograft adventitia 7 days after transplantation but not thereafter. More monocyte/macrophages (OX42) were also present in RCMV-infected allografts, but the difference was not significant. Concomitantly, RCMV infection significantly enhanced (P < .05) the expression of major histocompatibility complex class II (OX6) and almost doubled (P = NS) the expression of interleukin-2R (CD25), intercellular adhesion molecule-1 (CD54;1A29), and lymphocyte function-associated antigen-1 alpha-chain (CD11a; WT.1) in the adventitial inflammatory infiltrate. RCMV infection was linked with an early, prominent expression of both PDGF-BB mRNA at 7 days (P < .05) and at 1 month (P < .025) and of transforming growth factor-beta 1 mRNA at 7 days (P < .025) and at 1 month (P < .025) after transplantation. A less-prominent mRNA upregulation of acidic fibroblast growth factor (P < .05) was associated with RCMV infection at 7 days and at 1 month, as well as of epidermal growth factor at 1 month after transplantation, when compared with noninfected allografts, although the mRNA expression in both groups was below the levels of nontransplanted DA aortas. RCMV infection almost doubled basic fibroblast growth factor mRNA expression (P = NS) in the allograft vascular wall at 7 days and at 1 month. RCMV infection had no additional impact on insulin-like growth factor-1 mRNA expression when compared with noninfected allografts.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Cytomegalovirus infection enhances mRNA expression of platelet-derived growth factor-BB and transforming growth factor-beta 1 in rat aortic allografts. Possible mechanism for cytomegalovirus-enhanced graft arteriosclerosis. 798 Nov 94

Patients with one type of major histocompatibility complex class II combined immunodeficiency have mutations in a gene termed class II transactivator (CIITA), which coordinately controls the transcription of the three major human class II genes, HLA-DR, -DQ, and -DP. However, the experimentally derived B-lymphoblastoid cell line, clone 13, expresses high levels of HLADQ in the absence of HLA-DR and HLA-DP, despite its mapping by complementation analysis to this group. It was possible that one of the clone 13 CIITA alleles bore a mutation that allowed HLA-DQ, but not HLA-DR or -DP transcription. Alternatively, another factor, distinct from CIITA, might control HLA-DQ expression. We report here that ectopic expression of CIITA cDNAs derived by reverse transcriptase polymerase chain reaction from clone 13 do not restore expression of HLA-DQ in another CIITA-deficient cell line, RJ2.2.5. In addition, no CIITA protein is detectable in clone 13 nuclear extracts. In contrast, somatic cell fusion between clone 13 and RJ2.2.5 restored expression of the HLA-DQ haplotype encoded by the RJ2.2.5 DQB gene. Taken together, these data demonstrate the existence of an HLA-DQ isotype-specific trans-acting factor, which functions independently of CIITA.
 ...
PMID:An isotype-specific activator of major histocompatibility complex (MHC) class II genes that is independent of class II transactivator. 916 18

A unique subset of gammadelta T cells, termed dendritic epidermal T cells, reside in murine epidermis. It was previously reported that freshly isolated dendritic epidermal T cells and dendritic epidermal T cell lines expressed mRNA for interferon-gamma. Recent studies indicated that interleukin-18, a novel cytokine which strongly induces interferon-gamma production by T cells, was produced by murine keratinocytes and Langerhans cells. Interleukin-12, which is regarded as a key cytokine for Th1 type helper clone responses, has also been reported to be produced by these cells in murine skin. In this study, we demonstrated by enzyme-linked immunosorbent assay that interleukin-18 and interleukin-12 synergistically upregulated interferon-gamma production by dendritic epidermal T cells in short-term cultures. This was the case in both C57/BL6 mice and BALB/C mice, although the quantity of interferon-gamma produced was different in the two mouse strains. Interleukin-18 or interleukin-12 alone did not induce interferon-gamma production by dendritic epidermal T cells. Interferon-gamma mRNA was only weakly detected by the semiquantitative reverse transcriptase-polymerase chain reaction method in freshly isolated dendritic epidermal T cells, and the mRNA expression was much increased 12 h after stimulation with interleukin-18 and interleukin-12. We also confirmed biologic activity of interferon-gamma produced by dendritic epidermal T cells by showing upregulation of major histocompatibility complex class II expression on Pam 212, murine keratinocyte cell line. Thus, this study suggests that interleukin-18 and interleukin-12 produced by keratinocytes and Langerhans cells regulate interferon-gamma production by dendritic epidermal T cells and thus may play important parts in the regulation of immune responses in skin-associated lymphoid tissues.
 ...
PMID:Interleukins 18 and 12 synergistically upregulate interferon-gamma production by murine dendritic epidermal T cells. 1046 33

It has been reported previously that in vitro treatment of human blood derived dendritic cells (DC) with contact allergens provokes the elevated expression of mRNA for interleukin (IL) 1beta, under conditions where similar treatment of cells with the non-sensitizing skin irritant sodium lauryl sulfate (SLS) did not alter IL-1beta mRNA levels (Reutter et al., 1997). The purpose of the present investigation was to evaluate further this phenomenon and to explore the potential utility of this approach for the purpose of skin sensitization testing. Human peripheral blood progenitor cells prepared from healthy adult volunteers were cultured in the presence of IL-4 and granulocyte/macrophage colony stimulating factor. After 5 days of culture, the majority of cells had a Langerhans cell-like phenotype, with characteristic dendritic morphology and cell surface expression of CD83, major histocompatibility complex class II and CD1a determinants. These blood-derived DC were cultured in the presence of the contact allergen 2,4-dinitrofluorobenzene (DNFB), SLS or vehicle alone and mRNA expression for IL-1beta, IL-6 and IL-18 was analysed by semiquantitative reverse transcriptase polymerase chain reaction. Constitutive expression of all three cytokines was observed for DC isolated from all donors examined. Exposure to DNFB resulted in upregulation of IL-1beta mRNA (two- to threefold) in cells derived from three out of eight donors whereas IL-6 and IL-18 were largely unaffected by allergen exposure. In contrast, SLS treatment did not induce IL-1beta mRNA expression in any of the donors investigated. Analysis of cytokine mRNA expression using the protocol described by Reutter et al. (1997), did not increase the sensitivity of measurement of induced cytokine expression. Although selected upregulation of IL-1beta by blood derived DC has been confirmed, a wider range of contact allergens and irritants need to be assessed before this approach could be considered for hazard identification.
 ...
PMID:Investigation of induced changes in interleukin 1beta mRNA expression by cultured human dendritic cells as an in vitro approach to skin sensitization testing. 1090 42

Interleukin-18 (IL-18) is an important cytokine in innate immunity and in the induction phase of autoimmunity. We report the expression of IL-18 mRNA and protein after nerve crush during Wallerian degeneration (WD) of the rat nervous system. In normal optic nerves (ON) constitutive IL-18 mRNA levels as revealed by semiquantitative reverse transcriptase polymerase chain reaction were higher than in sciatic nerves (SN). After nerve crush, steady-state levels moderately increased in the distal nerve part of the SN but not the ON. By immunocytochemistry no SN or faint ON IL-18 protein expression was detectable in normal nerves. In contrast, IL-18 expression dramatically increased after SN and ON crush. On the cellular level, ED1(+) macrophages infiltrating the crush site strongly expressed IL-18 at days 2 and 4 after SN crush. By days 4 and 8, in addition, the entire distal nerve part was covered by IL-18(+) macrophages. At day 16, IL-18 immunoreactivity had disappeared despite the persistence of large numbers of ED1(+) macrophages. A similar infiltration of IL-18(+) macrophages was seen at the crush site in the ON. Moreover, microglia in the distal ON stump lacking macrophage infiltration and undergoing delayed myelin degradation up-regulated IL-18. In conclusion this study shows that IL-18 is involved in the cytokine network associated with the robust inflammatory response during WD of the SN. Despite up-regulation of the proinflammatory cytokine IL-18, major histocompatibility complex class II, and CD4 molecules similar to macrophages in the PNS, microglial activation after ON injury appears to be insufficient to mount an effective phagocytic response as a prerequisite for successful regeneration in the CNS.
 ...
PMID:Induction of the proinflammatory cytokine interleukin-18 by axonal injury. 1149 69

Through the regulation of human leukocyte antigen (HLA)-DM (DM) in B cells, HLA-DO (DO) modulates positively or negatively the presentation of specific peptides. Transduction of DO into human blood monocyte-derived dendritic cells (MoDC) has been proposed as a mean of modifying the peptide repertoire of major histocompatibility complex class II molecules. However, maturation of DC induced by inflammatory stimuli or possibly the adenoviral vector itself triggers acidification of vesicles and shuts down transcription of the class II transactivator gene as well as de novo biosynthesis of class II-related molecules and DM activity. In these conditions, it is unclear that transduced DO could alter the peptide repertoire. Our Western blot and reverse transcriptase-polymerase chain reaction analyses revealed that human DC derived from blood monocytes express small amounts of DOalpha. Transduction of DObeta alone resulted in the accumulation of a small pool of DO in DM(+) CD63(+) vesicles and at the plasma membrane of mature DC. The cell-surface increase in class II-associated invariant chain peptide (CLIP)/class II complexes is in line with an inhibitory role of DO on DM. Cotransduction of DOalpha and DObeta only slightly increased CLIP and DO levels at the cell surface. Together with the fact that a large fraction of transduced DO remains in the endoplasmic reticulum, this suggests that DM is limiting in these conditions. DO expression did not affect a mixed lymphocyte reaction but reduced presentation of the exogenous gp100 antigen to a specific T cell clone. These results show that transduced DO modulates antigen presentation in human mature MoDC, evoking the possible use of this chaperone for immunotherapy.
 ...
PMID:HLA-DO transduced in human monocyte-derived dendritic cells modulates MHC class II antigen processing. 1581 6

Canine distemper virus (CDV) infection of the central nervous system results in lesions of the gray and white matter. While a biphasic disease process has been discussed for leukoencephalitis with a prominent loss of viral protein expression, polioencephalitis has been associated with virus persistence. Using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), expression of pro- and anti-inflammatory cytokines such as interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF)-alpha, interferon (IFN)-gamma, and transforming growth factor (TGF)-beta were studied in the cerebra of distemper dogs with white matter lesions in the cerebellum. Additionally, cytokine values were correlated with the degree of CDV infection, major histocompatibility complex class II (MHC II) expression, and infiltration of CD4-, CD8-, and CD3epsilon-positive lymphocytes. Cerebral CDV infection was not associated with detectable light microscopic lesions or infiltration of B and T lymphocytes. However, an increasing number of CDV-antigen-positive cells was associated with an upregulation of MHC II antigen. RT-PCR results revealed a significant upregulation of IL-6, IL-8, IL-12, and TNF-alpha in the cerebra of distemper dogs, whereas IL-10 and TGF-beta showed no significant increase. Elevated cytokine values were directly related to the presence of CDV antigen and MHC II upregulation. However, succeeding increases of the latter did not result in an additional proportional elevation of cytokine expression values. In summary, the present study demonstrates the expression of pro-inflammatory cytokines by resident neural cells following CDV infection. Furthermore, the lack of light microscopic changes indicates that additional factors besides cytokines are necessary for the development of a distemper-characteristic neuropathology.
 ...
PMID:Increase of pro-inflammatory cytokine expression in non-demyelinating early cerebral lesions in nervous canine distemper. 1911 29