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)

A basal cell carcinoma (BCC) cell line (BCC-1/KMC) has recently been successfully established from a patient. The production of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6 and IL-8 was assessed in comparison with that of cultured normal keratinocytes. The mRNA expression of these cytokines was measured by a reverse transcriptase-polymerase chain reaction (RT-PCR) method and the protein production by an ELISA. The cultured BCC cells spontaneously secreted more IL-6 and IL-8 but less IL-1 than the keratinocytes after culture for 24 h at 37 degrees C. It is suggested that the increased expression of IL-6 and IL-8 may indicate the transformation of normal keratinocytes to locally aggressive BCC.
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PMID:The expression of cytokines by an established basal cell carcinoma cell line (BCC-1/KMC) compared with cultured normal keratinocytes. 896 85

The nuclear factor kappaB (NF-kappaB) regulates the transcription of genes bearing the kappaB consensus motif. Transmigration of NF-kappaB from the cytoplasm to the nucleus is regulated by the IkappaB family of inhibitory NF-kappaB-binding proteins. Dissociation of the NF-kappaB-IkappaB complex requires both phosphorylation and degradation of IkappaBs. We demonstrate that IL-1beta induces complete IkappaB alpha degradation in Caco-2 cell lines but not in HT-29, T84, SW-480 transformed cell lines, or native colonic epithelial cells. A similar lack of IkappaB alpha degradation in HT-29 cells followed TNF-alpha and bacterial polymer stimulation. IL-1beta stimulated NF-kappaB nuclear translocation and NF-kappaB-dependent IL-1beta and IL-8 expression in both Caco-2 and HT-29 cells as assayed by electrophoretic mobility shift assay, immunofluorescence, kappaB-luciferase transfection, reverse transcriptase-PCR analysis and ELISA. In HT-29 cells stimulated with IL-1beta, IkappaB alpha was phosphorylated and when cycloheximide blocked new protein synthesis, IkappaB alpha was partially degraded. NF-kappaB cytoplasmic to nuclear transmigration was incomplete and preceded IkappaB alpha degradation in 9T-29 cells, in contrast to complete coordinated NF-kappaB nuclear translocation and IkappaB alpha degradation in Caco-2 cells. Greater sensitivity of HT-29 cells to a calpain inhibitor, as measured by IL-8 secretion, suggested enhanced resistance to IkappaB alpha proteolysis. These data show that IL-1beta induces NF-kappaB activity and expression of NF-kappaB-dependent genes in colonic epithelial cells and suggest altered regulation of IkappaB alpha degradation compared with other cell lineages, which may result in their increased responsiveness to therapeutic blockade.
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PMID:Evidence for altered regulation of I kappa B alpha degradation in human colonic epithelial cells. 897 94

The persistence of human papillomavirus at cutaneous sites may be due to impaired trafficking of immune effector cells to the epidermis. We investigated whether HPV infection modulates cytokine mRNA expression in skin, thereby influencing local immunity. The mRNA expression of tumour necrosis factor-alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist (IL-1ra), IL-4, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor, transforming growth factor-beta, interferon-gamma and amphiregulin were assayed in cutaneous warts and normal skin by semiquantitative reverse transcriptase-polymerase chain reaction. The expression of the cytokines was heterogeneous in the specimens but, of the 12 mRNA species investigated, only IL-10 mRNA was significantly downregulated in warts compared with normal skin (P = 0.002). IL-1 alpha mRNA expression was significantly upregulated in common warts (P = 0.019) and plantar warts (P = 0.003) compared with normal skin. The expression of IL-1 alpha and IL-1ra mRNAs were significantly correlated in plantar warts (P < 0.05). Warts expressing IL-1 alpha also expressed amphiregulin, and there was a significant correlation between the expression of these two genes (P < 0.05). It is possible that IL-1 alpha expression in cutaneous warts may modulate the growth of papillomavirus-infected keratinocytes, mediated by amphiregulin, thus ensuring viral persistence.
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PMID:Cytokine mRNA expression in cutaneous warts: induction of interleukin-1 alpha. 901 32

Eosinophils are believed to be one of the important sources of cytokines at the site of allergic inflammation. A novel antiallergic agent epinastine showed a dose- and time-dependent suppressive effect on IL-8, one of the chemokines for eosinophils, released from eosinophils isolated from atopic diseases. The time-dependent accumulation of IL-8 inhibited by cycloheximide and the evaluation of the IL-8 mRNA levels by reverse transcriptase-polymerase chain reaction suggested that its action occurred in the posttranscriptional processes. It was suggested that epinastine might prevent the autocrine cycle for recruitment of human eosinophils by inhibiting IL-8 release from these cells.
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PMID:A novel antiallergic drug epinastine inhibits IL-8 release from human eosinophils. 902 26

The host-tumor interaction may play an important role in determining tumor progress. Recent studies have shown that this interaction can be influenced by the release of soluble factors by tumor cells and tumor-infiltrating lymphocytes (TIL). The aim of our study is to characterize the nature of cytokines and growth factors and their relationship to the cellular infiltrates in 16 patients with ovarian cancer using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Total RNA from 20 malignant and 10 benign specimens were used to assay for expression of 12 cytokines. Additionally, monoclonal antibodies (MAbs) were used to detect T cells, CD4+ helper and CD8+ cytotoxic/suppressor T-cell subtypes, B cells, and macrophages. Our results showed the expression of transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in 19, 17, and 10 malignant specimens, P < .001, .001, and .05, respectively. Other cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), TNF-beta/LT, IL-2, and IL-6 were expressed in a few cases, and IL-1alpha and IL-4 expression were not detected. The benign samples did not express IL-10, but GM-CSF, TGF-beta1, and IL-8 were expressed in one, one, and four specimens, respectively. Interestingly, in four cases in which samples from the primary and relapse tumors were available for analysis, the tumors in relapse showed a significant increase for TGF-beta1 (P < .05) and a decreased trend in IL-10 mRNA levels. The source of these factors was tumor cells as detected immunohistochemically. This combined alteration of TGF-beta1 and IL-10 was associated with a significant reduction in number of TIL in general, and CD8+ and macrophages in particular (P = .036 and .049, respectively). Our findings suggest the important role of certain soluble factors in the complex process of tumor progression. Furthermore, understanding the tumor-host relationship and the factors influencing the interaction may be helpful in developing effective and innovative treatment methods.
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PMID:Tumor-host interaction: analysis of cytokines, growth factors, and tumor-infiltrating lymphocytes in ovarian carcinomas. 904 97

Using reverse transcriptase polymerase chain reaction we showed that freshly plucked human anagen hair expressed both type 1 (80 kD) and type 2 (60 kD) interleukin (IL)-1 receptor mRNAs. The IL-1 receptor type 1 was functional since after in vitro stimulation of plucked hair with IL-1 alpha, we observed the induction of mRNA(s) for the inflammatory cytokines IL-1 beta, tumour necrosis factor alpha and IL-6 as well as for the chemokines monocyte chemotactic and activating factor and IL-8. In addition, the growth of dissected human anagen hairs in culture in vitro was significantly and dose-dependently inhibited by IL-1 alpha as a consequence of hair bulb degradation. These observations, together with those of other authors in IL-1 alpha transgenic mice evidence the inhibitory role of IL-1 on human hair growth. Therefore, in order to identify individuals with high inflammatory potential in their hair follicle environment, we designed a rapid and simple assay to detect variations in the level of IL-1 alpha production in the overnight supernatant of plucked hairs in culture. We observed that 32.7% of the specimens from the volunteers tested (n = 116) could be considered highly inflammatory in terms of IL-1 alpha production. Altogether, these results suggest that in alopecia androgenetica, hair growth might be negatively influenced by IL-1, directly produced by the outer root sheath keratinocytes. Consequently, identifying the "inflammatory alopecic individual' might be of clinical interest to discriminate among individuals for whom anti-IL-1 strategies might be of therapeutic relevance.
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PMID:Pro-inflammatory cytokine cascade in human plucked hair. 905 57

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.
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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

We studied the effects of serine proteases on cytokine gene expression by cultured normal human keratinocytes. In resting keratinocytes, steady-state mRNA levels for interleukins IL-1 alpha, IL-1 beta, IL-7, and IL-8, transforming growth factors alpha and beta, and tumor necrosis alpha were sufficient to be detected by our reverse transcriptase-polymerase clozin reaction method. Incubation of keratinocytes with 25 nM trypsin or 1 unit/ml thrombin for 24 hr selectively upregulated mRNA levels for granulocyte-macrophage colony-stimulating factor (GM-CSF) and Il-6 to detectable levels. Keratinocytes secreted GM-CSF and IL-6 protein in response to these proteases. Monensin did not inhibit the gene expression for the cytokines, thereby excluding the possibility of intervention by secreted molecules. Aprotinin and argatroban inhibited the effects of the proteases. SFLLRN and SLIGRL, tethered ligand receptor peptides for thrombin receptor and for proteinase-activated receptor 2 (PAR-2), respectively, duplicated the effects of the proteases on keratinocytes, which expressed mRNA for both receptors. Trypsin increased tyrosine phosphorylated proteins and intracellular free calcium concentrations. Tyrphostin, pertussis toxin, or H-7 suppressed trypsin- and thrombin-induced GM-CSF gene expression. Our results demonstrate that the serine proteases activate thrombin receptors and PAR-2 on keratinocytes, triggering intracellular signaling and then inducing the synthesis of GM-CSF. We speculate that serine proteases modulate the course of physiological and pathological processes in the skin by stimulating keratinocytes to produce the cytokines.
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PMID:Thrombin and trypsin induce granulocyte-macrophage colony-stimulating factor and interleukin-6 gene expression in cultured normal human keratinocytes. 906 88

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.
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PMID:Selective expression of the interleukin-2 gene discriminates between the auto- and allo-mixed lymphocyte reaction. 910 32

The gram-positive bacterium Streptococcus pyogenes (group A streptococcus) is the causative agent of a wide variety of suppurative infections of cutaneous tissues. Previous analyses have demonstrated that the M protein of S. pyogenes is an adhesin that directs the attachment of the streptococcus to keratinocytes in the skin. In this study, we have examined keratinocyte function in response to S. pyogenes and found that adherent versus nonadherent streptococci promote distinct patterns of expression of several proinflammatory molecules and keratinocyte cell fate. When analyzed by a quantitative reverse transcriptase PCR method, infection of cultured HaCaT keratinocytes with adherent, but not nonadherent, streptococci resulted in increased expression of mRNA for the cytokines interleukin-1alpha (IL-1alpha), IL-1beta, and IL-8 but neither infection induced expression of tumor necrosis factor alpha. In contrast, both adherent and nonadherent S. pyogenes induced expression of IL-6 and each promoted synthesis and release of prostaglandin E2 (PGE2). However, considerably greater levels of IL-6 expression were stimulated by adherent streptococci relative to nonadherent streptococci and the kinetics of PGE2 release in response to nonadherent streptococci was delayed compared to the response to adherent streptococci. Staining with the fluorescent probe ethidium homodimer-1 revealed that keratinocyte membranes were rapidly damaged upon infection with adherent streptococci but were not damaged by nonadherent streptococci. Finally, treatments which inhibited streptococcal metabolism completely blocked the ability of adherent streptococci to elicit responses. These data suggest that expression of an adhesin is a strategy used by S. pyogenes to modulate keratinocyte responses during infection of the skin and implicate additional streptococcal products in these signaling interactions.
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PMID:Keratinocyte proinflammatory responses to adherent and nonadherent group A streptococci. 916 41


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