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T Schwarz

Publications and source records attributed to T Schwarz.

At least 163 records · Page 9Linked to original sources
PubMed1996

Interleukin-12 prevents ultraviolet B-induced local immunosuppression and overcomes UVB-induced tolerance.

Ultraviolet (UV) light abrogates contact hypersensitivity (CHS) responses and induces hapten-specific tolerance. Because Th-1 cells are critically involved in CHS and are induced to develop by the cytokine interleukin (IL)-12, we asked whether IL-12 might overcome UV-induced local immunosuppression. C3H/HeN mice exposed to low doses of UV light over 4 d and hapten sensitized through the irradiated skin area with dinitrofluorobenzene showed profound inhibition of the CHS response, which was completely prevented upon intraperitoneal injection of murine recombinant IL-12 (rIL-12) after the last UV exposure. UV-treated mice resensitized 14 d after the first challenge displayed hapten-specific tolerance, whereas UV-exposed mice injected with rIL-12 before the first sensitization exhibited a vigorous CHS response. Furthermore, mice that were initially sensitized through UV-exposed skin also produced a significant CHS reaction when they received rIL-12 before resensitization. Adoptive transfer of spleen and lymph node cells from UV-irradiated mice treated with rIL-12 had no effect on the CHS response in recipient mice, whereas transfer of cells from UV-treated mice inhibited the immune response. These findings demonstrate that rIL-12 can prevent UV-induced local immunosuppression and overcome UV-induced hapten-specific tolerance.

Animals↗
PubMed1996

Transforming growth factor-alpha induces interleukin-6 in the human keratinocyte cell line HaCaT mainly by transcriptional activation.

There is ample evidence that several cytokines, including transforming growth factor-alpha (TGF-alpha), interleukin (IL)-6, and IL-8 are upregulated in psoriasis, suggesting a pathogenic role for these cytokines. The sequence of these events, however, has not been elucidated. Recently it has been reported that TGF-alpha induces IL-6 in thymocytes through posttranscriptional regulation; therefore, we were interested in whether TGF-alpha can also induce IL-6 in human keratinocytes. Thus, we stimulated the human keratinocyte cell line HaCaT with TGF-alpha and tested supernatants for IL-6 activity. TGF-alpha resulted in a significant induction of the release of IL-6. This was also confirmed by northern blot analysis, which revealed a transient increase in IL-6 mRNA. This increase was unlikely due to enhanced mRNA stability, because we could not observe induction of IL-6 -specific transcripts by TGF-alpha in the presence of actinomycin D. To determine whether IL-6 induction by TGF-alpha is transcriptionally regulated, we transfected fragments of the IL-6 upstream region, subcloned into a plasmid just upstream of the chloramphenicol acetyl transferase coding region, into HaCaT cells. A 238-bp fragment and a 123-bp fragment, both containing nuclear factor (NF)-IL-6 and NFkappaB sites, exhibited significant induction of chloramphenicol acetyl transferase activity upon treatment with TGF-alpha. Because IL-6 transcription is known to be regulated by activation of NFkappaB and NF-IL-6, we analyzed the activation of these DNA-binding proteins by electrophoretic mobility shift assays. NF-IL-6 binding to a 32P-labeled NF-IL-6 binding sequence was enhanced 20 min after TGF-alpha stimulation and returned to basal levels within 90 min, whereas NFkappaB binding activity was enhanced after 20 min and returned to normal 60 min after stimulation. We conclude that TGF-alpha induces IL-6 in HaCaT cells and, in contrast to thymocytes, may do so by transcriptional activation, possibly through activation of NFkappaB and NF-IL-6.

Base Sequence↗
PubMed1996

[Metal dermatoses I].

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Dermatitis, Allergic Contact↗
PubMed1996

Stimulation of cytokine production via a special standardized mistletoe preparation in an in vitro human skin bioassay.

The mistletoe preparation Lektinol is standardized with respect to bioactive mistletoe lectin, the active component of mistletoe. This standardized mistletoe preparation and its active components (mistletoe lectins) were compared in the skin2 bioassay in vitro for their capacity to stimulate interleukin 1 alpha and interleukin 6 release from skin analogue tissue, composed of human cells in their naturally secreted matrix. The standardized mistletoe preparation, its basic ingredient, aqueous mistletoe extract, and pure mistletoe lectins all stimulated IL-1 alpha and IL-6 release from skin2 tissues during 24 h incubation. The amounts of cytokines released from various skin2 tissue lots by mistletoe lectin I (ML I) (0.75-8.0 ng/ml) and by the standardized mistletoe preparation remained relatively constant across a series of different batches. Concentration-response curves to the standardized mistletoe preparation and ML I were similar for IL-1 alpha and IL-6 release. The importance of the concentration of mistletoe lectins for the cytokine-releasing action of the standardized mistletoe preparation was confirmed using a neutralizing anti-mistletoe lectin antiserum. CONCLUSIONS. Using the skin2 method it was shown that reproducible stimulation of cytokine release by a standardized mistletoe preparation from batch to batch is one of the notable features of its pharmaceutical quality. This standardized mistletoe preparation therefore represents a preparation with constant immunobiological effects. Mistletoe lectins of the standardized mistletoe preparation are the active substances in the skin2 bioassay. The skin2 method is a reliable quantitative bioassay for determination of immunopharmacological effects.

Biological Assay↗
PubMed1996

Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity.

At first sight, the pathophysiology of contact hypersensitivity (CHS) seems to be well understood. Whereas this may apply to some extent to the sensitization phase of CHS, very little is actually known about the elicitation phase of this response. Although the mechanisms of T-cell priming (sensitization) may be more interesting for immunologists, those involved in the elicitation of T cell-mediated secondary responses are more relevant for clinical management because clinically manifest allergic contact dermatitis always reflects the effector phase of CHS. This review summarizes the role of different cellular components and soluble mediators on the elicitation of CHS. In addition, recent studies revealed that, besides selective activation of antigen-specific T cells, epicutaneous application of haptens has a number of direct effects on the cutaneous immune system. The most relevant of these are induction of cytokine and chemokine secretion and endothelial activation. In an attempt to integrate data on this issue, it is proposed that the capacity of contact allergens to directly induce proinflammatory signals in the skin is of relevance and perhaps essential for elicitation of clinically manifest CHS responses. Moreover, the proinflammatory effect of allergens themselves may explain the strict dose dependency of CHS responses and the relatively high concentrations of allergens needed for elicitation of CHS because allergens evoke nonspecific irritation only when applied in relatively concentrated form.

Allergens↗
PubMed1996

Stimulation of neutropoiesis by a special standardized mistletoe preparation after cyclophosphamide chemotherapy in mice.

Lektinol, is a special mistletoe preparation (SMP) with immunostimulatory activity, standardized with respect to bioactive mistletoe lectin, one of the most active components of mistletoe. In the present study, stimulation of leukopoiesis by SMP was investigated in mice after induction of myelosuppression by the cytostatic agent cyclophosphamide (CP). Under the experimental conditions described, CP induced severe leukopenia followed by a recovery phase where leukopoiesis was distinctly enhanced in mice treated additionally with SMP at daily intravenous doses in a range of 30 to 5000 microliters/kg body weight. This phenomenon was mainly due to a stimulation of granulopoiesis resulting in a stronger increase of metamyelocyte and mature neutrophil counts in the peripheral blood.

Animals↗
PubMed1995

Removal of the majority of epidermal Langerhans cells by topical or systemic steroid application enhances the effector phase of murine contact hypersensitivity.

Whereas epidermal Langerhans cells (LC) are thought to be the principal APCs for initiation of contact hypersensitivity (CHS) responses, their role as APC in the effector phase of CHS is still unclear. It is currently thought that LC elicit the CHS response by presenting Ag to trafficking Ag-specific T cells within the skin. To test this hypothesis, we removed the majority of resident LC at the site of CHS challenge by topical application of various steroid creams to one ear in BALB/c mice (> 85% LC depletion). Either 2 days before or 4 days after steroid treatment of the ear, mice were sensitized on the abdomen with the hapten trinitrophenyl and challenged 10 days later at the steroid-pretreated ear. At that time point, direct anti-inflammatory effects of the steroid were no longer present. Surprisingly, CHS responses were markedly stronger at the sites of prior steroid application when compared with vehicle-treated controls, indicating that depletion of most of the resident LC not only fails to impair, but enhances, the expression of CHS significantly. UV irradiation or application of croton oil at the challenge site, as well as systemic steroid application, all of which are alternative methods of diminishing the number of epidermal LC, also significantly up-regulated CHS. In contrast, irritant dermatitis and sensitization or elicitation of CHS in steroid-treated mice at distant sites, as well as delayed-type hypersensitivity responses against the same hapten, were unaffected by topical steroid pretreatment. In conclusion, our data suggest that resident LC are not the relevant APC in the effector phase of CHS and that they may even provide down-regulatory, rather than stimulatory, signals during elicitation of CHS.

Administration, Topical↗
PubMed1995

Functional analysis of a newly identified TAAT-box of the rat insulin-II gene promoter.

Transcriptional regulation of insulin gene expression is achieved by an interplay of tissue-specific and ubiquitous cis- and trans-acting elements. E-box like motifs and TAAT-motifs were shown to play a crucial role in initiating insulin gene transcription. Studying the AT-rich region of the rat insulin-II promoter between nucleotides -212 and -196, we observed a base difference at -211, an adenosine instead of a cytidine, compared to the previously reported sequence (EMBL Accession No. J00748). Sequence analysis of promoter fragments from different rat strains showed that adenosine at position -211 represents the wild type (EMBL Accession No. X82162). This base exchange leads to the formation of an additional TAAT-motif, i.e. TAAT3, at the complementary DNA strand directly upstream of the previously studied TAAT2 motif, formerly named CT-2. Here we show that the newly identified motif TAAT3 is involved in (i) transcriptional control in vivo, (ii) in vitro DNA/protein interactions, and that (iii) TAAT1, TAAT2 and TAAT3 are binding sites for the homeodomain-containing factor IPF-1.

Adenosine↗
PubMed1995

[Scarring psoriatic alopecia].

Temporary hair loss is well accepted as a possible result of psoriatic plaques. On the other hand, it is still a controversial issue whether psoriasis can cause scarring alopecia. The following report presents a 38-year-old woman who had been suffering from progressive hair loss from chronic psoriatic plaques of the scalp for some years. Clinical examination revealed an area of scarring alopecia in association with typical features of psoriasis. Histology showed a cord-like fibrosis replacing former hair follicles, a perivascular lymphohistiocytic infiltrate in the upper dermis occasionally invading the follicular epithelium, and characteristic features of psoriasis of the scalp. The clinical course and the lack of evidence for any other causes of scarring alopecia suggest an aetiopathogenetic link between psoriasis and scarring alopecia. Knowledge of this relationship appears to be of practical significance, since efficient antipsoriatic therapy can stop hair loss and thus may be able to prevent scarring.

Adult↗
PubMed1995

Successful treatment of generalized lichen planus with recombinant interferon alfa-2b.

Three patients with generalized lichen planus were treated with interferon alfa-2b. The therapy was tolerated well by all patients with only minor side effects. A response was observed within 2 to 3 weeks. Itching and erythema decreased first, followed by gradual flattening and disappearance of papules and plaques after 8 to 10 weeks of treatment. After 12 weeks, therapy was discontinued after stepwise dosage reduction. In two patients, minor lesions recurred during dosage reduction. Both flares were controlled by readministration of interferon.

Adult↗
PubMed1995

Relapsing linear acantholytic dermatosis.

The case of an 81-year-old man with relapsing linear acantholytic dermatosis is described. This is the second description of this disease entity, which is characterized by the histopathologic and ultrastructural features of Hailey-Hailey disease. Clinically, it is characterized by skin lesions that wax and wane in a systematic pattern following the lines of Blaschko.

Abdomen↗
PubMed1995

Ultraviolet-B-induced apoptosis of keratinocytes: evidence for partial involvement of tumor necrosis factor-alpha in the formation of sunburn cells.

Irradiation with ultraviolet (UV) B radiation results in the formation of apoptotic keratinocytes called sunburn cells. Recently, it was demonstrated that keratinocytes can release tumor necrosis factor-alpha (TNF-alpha), which is known to cause apoptosis in particular cells. In addition, it has been shown that UVB light induces the release of TNF-alpha by keratinocytes and that keratinocytes express the 55-kD receptor for TNF-alpha. Therefore, we investigated whether TNF-alpha is involved in UV-induced apoptosis of keratinocytes. Normal human keratinocytes and HaCaT cells were exposed to UVB light, and apoptosis was examined by nick translation evaluated by fluorescence-activated cell sorter analysis. UVB induced apoptosis in a dose-dependent manner, which was confirmed by electron microscopy. Addition of a polyclonal antibody directed against human TNF-alpha immediately after UVB exposure was able to reduce DNA fragmentation. However, it was not possible to rescue all cells from apoptosis. To prove whether TNF-alpha is also involved in vivo in UVB-induced apoptosis of keratinocytes, Balb/c mice were exposed to UVB on their abdomens, skin biopsies were performed 24 h later, and sunburn cells were counted. A single dose of 2000 J/m2 caused a significant induction of sunburn cells. Subcutaneous injection of a polyclonal antibody directed against murine TNF-alpha immediately after UVB treatment resulted in a significant but incomplete reduction of sunburn cells, whereas injection of a rabbit IgG as a control had no effect. In both the in vitro and in vivo systems, application of recombinant TNF-alpha alone either to untreated keratinocytes or into normal murine skin did not induce sunburn cells. Thus, these data demonstrate that TNF-alpha is involved in UVB-induced apoptosis, but by itself is not able to induce sunburn cells. This further supports the notion that UVB-induced apoptosis of keratinocytes is a multifactorial event.

Animals↗
PubMed1995

Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts. Evidence for increased cell viability and suppression of cytokine release.

To elucidate cellular concepts for protection against ultraviolet (UV) light we investigated the effect of heat shock protein 70 (hsp70) overexpression on cell viability and on the secretion of UV-inducible immunological cytokines. Transfected murine fibrosarcoma cells (WEHI-S), overexpressing hsp70 or a sham transfected control were used. Overexpression of hsp70 was sufficient to markedly increase cell viability upon treatment with UVB (290-320 nm). Since long wave UV (UVA, 320-400 nm) as well as UVB turned out to stimulate the release of O2- radicals we studied the cell viability upon oxidative stress. Hsp70 overexpression increased viability upon treatment with hydrogen peroxide or menadione, but had no influence on UV-induced O2- release. UV-light is known to upregulate immunologic and proinflammatory cytokines such as IL-1 and IL-6. Oxidative stress appeared to exert a similar effect. Hsp70 overexpression markedly decreased the release of IL-6 induced by UVA, UVB and oxidative stress. To test whether the hsp70 mediated suppression is confined to events caused by UV-light we determined IL-1-mediated effects. IL-1-induced IL-6 release was reduced by hsp70 overexpression, whereas the IL-1 mediated activation of nuclear factor kappa B was not affected. Our data suggests that hsp70 plays a central role not only in cell protection against UV-light, but also in the regulation of proinflammatory cytokine release induced by UV-exposure.

Animals↗
PubMed1995

Maintenance ECT: indications and outcome.

Maintenance electroconvulsive therapy (M-ECT) is used to prevent recurrence of depression. Indications regarding patient selection criteria and efficacy are uncertain, in part because data are lacking. Comparison of M-ECT patients (N = 21) with controls demonstrates that M-ECT is chosen for patients whose course is characterized by multiple hospitalizations and failure to adequately respond to other therapies. M-ECT patients were exposed, on average, to 10 different psychotropic medications, including five trials of tricyclic antidepressants. Greater than half of their cumulative hospitalizations were for ECT. Their rate of rehospitalization decreased by 67% after institution of prophylactic M-ECT, demonstrating treatment efficacy. A tendency toward relapse and rehospitalization remains when M-ECT patients are compared to controls.

Adult↗