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 number of cytokines have previously been localised within the developing and adult hair follicle, however, the role they play in producing a mature hair follicle remains unknown. In an attempt to identify dermal papilla specific cytokines and thus those that may have an important controlling role, cytokine gene expression profiles, obtained by reverse transcriptase-polymerase chain reaction (RT-PCR), were compared between whole anagen rat hair follicles, passage 2 dermal papillae (a cell type with hair inductive capacity), and footpad fibroblasts (a non-hair inducing cell type). Based on this qualitative data, we were unable to identify a dermal papilla specific gene. The analysis of the pattern and timing of cytokine gene expression during the hair cycle is likely to be more informative. A semi-quantitative RT-PCR technique was therefore developed for studying trends in the level of in vivo expression of the following cytokines and their receptors from early anagen to early catagen in the rat hair growth cycle: insulin-like growth factor I, transforming growth factor beta 1, tumour necrosis factor, and basic fibroblast growth factor. These genes were found to be differentially expressed and this was correlated with their possible functions in controlling the hair growth cycle, providing valuable insights into the role of cytokines in regulating the hair growth process.
Exp Dermatol 1996 Aug
PMID:In vivo cytokine and receptor gene expression during the rat hair growth cycle. Analysis by semi-quantitative RT-PCR. 888 67

In order to investigate the role of staphylococcal enterotoxins in the pathogenesis of dermatitis in atopic patients, the growth and expression of T cell receptor V beta in peripheral blood mononuclear cells (PBMCs) from atopic dermatitis patients induced by stimulation with staphylococcal enterotoxin A (SEA) or staphylococcal enterotoxin B (SEB) were examined. Lymphocyte stimulation tests (LST) using SEA or SEB were performed in atopic dermatitis (AD) patients (n = 10) and normal controls (n = 5). PBMCs from AD patients displayed significantly stronger responses to SEA or SEB than those from the controls. To ascertain further whether SEA acts as a superantigen in atopic dermatitis, the expression of 22 genes in the variable region of the beta chain (V beta) of T cell receptors (TcR) was examined before and after stimulation with SEA by a reverse transcriptase-polymerase chain reaction (RT-PCR). Before stimulation, only weak expression of V beta was observed, and the expression of the various V beta segments was uniform in the normal controls (n = 3). In the AD patients (n = 3), the expression of V beta was enhanced, but was not uniform in 2 out of 3 patients and the pattern of expression was characteristic in each individual. This suggests that V beta expression varies in individual AD patients and displays restricted heterogeneity, reflecting the diversity of the etiology of the disease. After culture of the SEA-stimulated cells, no difference was observed in the expression of TcR V beta segments in the 3 normal controls as compared with that prior to stimulation, but particular V beta segments were intensely expressed in 3 AD patients, displaying distinct patterns (case I: V beta 9, V beta 10, V beta 18; case 2: V beta 6.1-3; case 3: V beta 6.1-3, V beta 18). Many of these V beta segments corresponded with those known to be induced by SEA. These results suggest oligoclonal proliferation of T cells in the peripheral blood of AD patients and high responsiveness in each clone, and since the expression of V beta segment after SEA stimulation was restricted, the actions of staphylococcal enterotoxins as superantigens were suggested.
J Dermatol Sci 1996 Oct
PMID:Role of staphylococcal enterotoxins in pathogenesis of atopic dermatitis: growth and expression of T cell receptor V beta of peripheral blood mononuclear cells stimulated by enterotoxins A and B. 890 55

GM-CSF together with IL-1 beta and TNF-alpha has been shown to play a key role in the maturation of LC in vitro. To investigate the presence of GM-CSF, IL-1 beta and TNF-alpha in human skin-derived lymph, we cannulated microsurgically a superficial lymph vessel on the lower leg of six healthy volunteers. Messenger RNA levels were estimated by a reverse transcriptase polymerase chain reaction (RT-PCR) method. From a total of 20 different samples, each consisting of 10(6) lymph cells, total RNA was extracted, reverse transcribed to cDNA and amplified using specific primers for the target gene. Amplified products were sized by electrophoresis and visualized by ethidium bromide. Specific transcripts for GM-CSF were detected in all lymph samples, indicating that circulating human skin-derived lymph cells express GM-CSF mRNA. A mean level of 11.5 +/- 2.1 pg/ml GM-CSF was detected in the lymph samples examined, as determined by a sensitive ELISA. In contrast to GM-CSF, occasional weak mRNA signals together with a mean level of 2.7 +/- 2.2 pg/ml were found for IL-1 beta, and neither specific transcripts nor protein were detected for TNF-alpha. Thus, our results demonstrate that afferent skin lymph cells constitutively express GM-CSF.
Arch Dermatol Res 1996 Oct
PMID:GM-CSF mRNA and protein in human skin-derived lymph. 893 64

Recent reports point to a role for interleukin-12 (IL-12) in regulating T- and NK-cell function, macrophage activation and initiation of Th1-type cell responses. We sought to determine whether CD1a+ dendritic cells of the skin, as major antigen-presenting cells, are a source of IL-12 and therefore important in the initiation of Th1-type cell responses. To investigate this hypothesis, we cannulated microsurgically a skin-draining lymph vessel in the lower legs of five healthy volunteers. Altogether, ten different samples, each consisting of 1 x 10(6) lymph cells, were investigated. In four of the ten samples. CD1a+ dendritic lymph cells were isolated and purified by positive selection using mouse anti-CD1a monoclonal antibodies and sheep anti-mouse antibody-coated Dynabeads. Messenger RNA levels were estimated using a nested reverse transcriptase polymerase chain reaction (nRT-PCR) method. Total RNA was extracted from the cells, reverse transcribed to cDNA and amplified using specific primers for the target gene. Amplified products were sized by electrophoresis and visualized by ethidium bromide. Expression of IL-12 p40 and p35 mRNA was detected in all samples, both whole lymph samples and the highly enriched CD1a+ dendritic cell population. Our findings demonstrate that human skin-derived CD1a+ dendritic lymph cells produce IL-12 mRNA and may therefore be an important source of IL-12. Thus one might speculate that these CD1a+ dendritic cells, through their IL-12-producing capacity, might significantly influence the balance of Th1 versus Th2 reactions ultimately occurring.
Arch Dermatol Res 1996 Feb
PMID:IL-12 gene expression in human skin-derived CD1a+ dendritic lymph cells. 893 85

The importance of nitric oxide (NO) in mediating macrophage functions has been demonstrated, but production of this potent gas has not been examined in Langerhans cells (LC). Using murine LC purified from epidermal cell suspensions and the recently established LC-like cell line derived from newborn BALB/c epidermis (XS-52), it was shown with reverse transcriptase (RT)-PCR that inducible nitric oxide synthase (iNOS) message is present in these cells. Murine keratinocytes did not contain iNOS message. iNOS mRNA was increased in a concentration-dependent manner by lipopolysaccharide (LPS) in purified murine LC and XS-52 cells, and immunofluorescence using an antibody to iNOS revealed bright cytoplasmic staining in LPS-treated XS-52 cells. Anti-iNOS antibody brightly stained LC on human neonatal foreskin cryosections. An increase in NO production by LPS-treated XS-52 cells over 16 h, as measured by the determination of nitrite levels in culture supernatants using the Griess Reaction, was observed. Interferon-gamma (IFNgamma) did not affect NO production on its own. In the presence of LPS and IFNgamma, NO production was 3 times more than observed with LPS alone. NO production was inhibited by the NOS inhibitor L-NAME. Western blots with anti-iNOS antibody demonstrated an increase in iNOS expression in LPS-treated XS-52 cells that was suppressed by IL-10. NO produced in LC may affect LC functions such as microbicidal activity, antigen presentation, and cytotoxicity and may affect adjacent keratinocytes and melanocytes.
J Invest Dermatol 1996 Dec
PMID:Langerhans cells express inducible nitric oxide synthase and produce nitric oxide. 894 67

Primary cutaneous CD30 (Ki-1)+ large cell lymphoma (KiL) and lymphomatoid papulosis (LyP) type A are collectively termed as primary cutaneous CD30-positive lymphoproliferative disorders. We examined the cytokine profile of skin-infiltrating cells and the therapeutic efficacy of recombinant interferon-gamma (rIFN-gamma) in primary cutaneous KiL and LyP type A. By reverse transcriptase-polymerase chain reaction, mRNAs for interleukin-4 (IL-4) and IL-10 were detected in the dermis of skin lesions in all cases (three cases of KiL and four cases of LyP). In addition, tissue from one KiL patient transcribed IL-2 and IFN-gamma messages, and one LyP patient showed IL-2 mRNA. In contrast, normal skin from ten healthy donors contained mRNA for IL-2 or IFN-gamma, or both, but not for IL-4. Before the therapeutic trial of rIFN-gamma, the response of skin lesions was assessed by a predictive skin test with local injection of rIFN-gamma (0.5 x 10(6) Japan Reference Units [JRU; 1 JRU roughly corresponds to 4 NIH units]) for 3 consecutive days in two KiL and two LyP patients. Numbers of skin-infiltrating CD30+ cells were decreased, and transcription of mRNA for IL-4 and IL-10 was downregulated after the skin test in one KiL and two LyP cases. One KiL patient showed no histologic response or change in mRNA expression. In the therapeutic trial, rIFN-gamma (total doses of 1.2-4.0 x 10(7) JRU) was administered intravenously (n = 2) or locally (n = 2). In three patients who responded to the skin test, the lesions were objectively improved and the numbers of skin-infiltrating CD30+ cells were markedly decreased after the therapeutic trial. No improvement was observed in one KiL patient who did not respond to the skin test. These findings suggest that the skin-infiltrating CD30+ cells in KiL and LyP have a Th2 cytokine profile and raise the possibility that the administration of rIFN-gamma improves the conditions by inhibiting cytokine mRNA transcription and proliferation of CD30+ cells.
J Invest Dermatol 1996 Dec
PMID:Th2 cytokine mRNA expression in primary cutaneous CD30-positive lymphoproliferative disorders: successful treatment with recombinant interferon-gamma. 894 69

Cytokines are believed to play an important role in the pathogenesis of cutaneous T cell lymphoma. Data regarding the local cytokine pattern in mycosis fungoides (MF) are partly conflicting. Recent studies have suggested a shift from type 1 to type 2 cytokine pattern because IL-4 and IL-5 mRNA have been more frequently detected in lesions of advanced stages. Another study has described a type 1 cytokine pattern in MF lesions. None of the previous studies of cytokine mRNA expression in MF, however, used quantitative methods, and therefore only the presence of a cytokine, but not the level of expression, could be determined. To gain better insight into the development of cytokine pattern during tumor progression we used semiquantitative reverse transcriptase-polymerase chain reaction to analyze cytokine mRNA expression in MF skin lesions at different stages. Biopsies from patients with patch (n = 11), plaque (n = 6), and tumor (n = 3) stage MF were compared with biopsies from patients with pleomorphic T cell lymphoma (n = 5), psoriasis (n = 7), atopic dermatitis (n = 5), and nonlesional skin (n = 8). MF progression was associated with significantly higher IL-10 and lower interferon-gamma mRNA expression. Moreover, the stage-dependent increase in IL-10 mRNA expression was also found in paired samples from individual patients. Unlike in pleomorphic T cell lymphoma, however, typical T helper 2 cells did not seem to be the source of increasing IL-10 in advanced MF, because stage-independent IL-4 mRNA was rarely detected, suggesting contribution of nonlymphoid cells to local IL-10 production. The overexpression of IL-10 in MF may be of importance for tumor progression, because this immunosuppressive cytokine might be involved in downregulation of immunologic tumor surveillance.
J Invest Dermatol 1996 Dec
PMID:Progression of mycosis fungoides is associated with increasing cutaneous expression of interleukin-10 mRNA. 894 70

Tissue homeostasis in skin is regulated by epithelial-mesenchymal interactions, mostly operating via diffusible factors. To study the underlying regulatory mechanisms, in vitro systems have been established to mimic the in vivo situation in skin. In co-cultures, keratinocytes grow either adjacent to irradiated fibroblasts on plastic or on top of collagen gels containing fibroblasts, thus forming 3-dimensional organotypic structures. Keratinocyte growth is supported in part by fibroblast-produced factors induced by keratinocyte mediators such as interleukin-1 (IL-1). To better understand this cellular interaction and its modulation by fibroblast proliferation and extracellular matrix (ECM), we examined the effect of IL-1 on growth factor expression in proliferating and growth-arrested x-irradiated human dermal fibroblasts on plastic and in resting cells embedded in collagen gels. By semiquantitative reverse transcriptase PCR, we demonstrated that IL-1alpha and IL-1beta stimulated the expression of KGF, HGF, IL-1alpha, IL-1beta, IL-1RI, and IL-8 in fibroblasts regardless of their physiologic condition, whereas that of TGF-beta remained unaffected. The constitutive mRNA levels were usually lower in irradiated postmitotic and ECM-embedded cells than in proliferating fibroblasts. Cells responded to stimulation with IL-1 under all three culture conditions, although to different degrees depending on the growth factor. As demonstrated for HGF, IL-8, and IL-1beta, the IL-1alpha-induced mRNA expression was followed by production and secretion of protein in irradiated fibroblasts. Thus, our findings show that resting and growth-inhibited fibroblasts, reflecting more closely the situation in dermis, exhibit lower constitutive growth factor expression levels but characteristically respond to IL-1 stimulation.
J Invest Dermatol 1996 Dec
PMID:Interleukin-1-induced growth factor expression in postmitotic and resting fibroblasts. 894 73

Since regulation of keratinocyte IL-1 receptor expression is likely to have a major impact on the biologic effects of IL-1 on epidermal cells, we examined expression, regulation, and function of IL-1R in cultured human keratinocytes. By reverse transcriptase polymerase chain reaction, human keratinocytes were shown to express IL-1 receptor type I (IL-1RI) and IL-1 receptor type II (IL-1RII). Human keratinocyte IL-1RI mRNA expression was dependent on the differentiation state of the cell and was regulated by ultraviolet B (UVB) radiation, which initially decreased but later increased IL-1RI expression. This UVB-induced biphasic modulation of IL-1RI expression was mediated by an autocrine mechanism involving endogenously produced IL-1alpha and IL-1RI. Increased expression of IL-1RI in UVB-irradiated or IL-1alpha-stimulated keratinocytes was functionally important, because it endowed these cells with the capacity to upregulate expression of the intercellular adhesion molecule (ICAM)-1 upon IL-1alpha stimulation. Keratinocyte IL-1RII expression was regulated by UVB irradiation in an inverse manner. Significant and rapid upregulation of IL-1RII was observed within 1 h after UVB irradiation and gradually decreased to background levels within 24 h. Inverse regulation of IL-1RII versus IL-1RI was associated with opposite functions, because blocking of IL-1RII enhanced IL-1alpha effects on induction of ICAM-1 expression. These studies demonstrate that IL-1 responsiveness of UVB-irradiated keratinocytes critically depends on regulation of IL-1RI expression and that IL-1RII serves as a "decoy" receptor for IL-1, limiting rather than promoting IL-1-mediated effects.
J Invest Dermatol 1996 Dec
PMID:Interleukin-1 receptors type I and type II are differentially regulated in human keratinocytes by ultraviolet B radiation. 894 76

Delayed type hypersensitivity (DTH) response to dermatophyte antigens is one of the host defense mechanisms in dermatophytosis. Skin lesions of dermatophytosis were examined for the cytokine mRNAs expression using the reverse transcriptase/polymerase chain reaction (RT-PCR) method. Interferon-gamma (IFN-gamma) mRNA was expressed in all of the dermatophytosis lesions. IFN-gamma plays an important role in the effector phase of the DTH reaction. Therefore, these findings indicate that DTH response is elicited in the skin lesions with dermatophytosis.
J Dermatol Sci 1996 Nov
PMID:Local expression of IFN-gamma mRNA in skin lesions of patients with dermatophytosis. 895 17


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