ISSN:1660-5527    

DOI:10.1159/000210935

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000210936

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000210937

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

There is laboratory and clinical evidence to suggest that retinoids have a potentially important place in the management of neoplastic and preneoplastic disorders of the epidermis. Topical administration avoids the side-effects of orally administered retinoids, but doubts remain over their efficacy. Evidence from clinical studies suggests that although topical retinoids have some effect in treating established skin cancers, alternative treatments are more effective. Topical retinoids appear more effective in the treatment of solar keratoses and epidermal dysplasia in photodamaged skin.

ISSN:1660-5527    

DOI:10.1159/000210938

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Cellular retinoid-binding proteins play an important physiological role in the mode of action of retinoids upstream from the nuclear receptors. Tritiated analogues of retinol (ROL) and retinoic acid corresponding to substituted benzo[b]thiophene (CD-270) alcohol and carboxylic acid, respectively, were used for the binding studies of the cellular retinoic acid-(CRABP-) and retinol-(CRBP-) binding proteins in human epidermal cells and serum retinol-binding protein (RBP). We show that [3H]CD-270 carboxylic acid binds specifically to CRABP, whereas the alcohol derivative binds strongly to CRBP. However, the low amount of CRABP present concomitantly with CRBP suggests that [3H]CD-270 alcohol might be oxidized into minute amounts of the corresponding carboxylic acid derivative. The acidic character of the alcohol goup due to the aromatic ring of CD-270 might also support a possible binding to CRABP. In contrast, both derivatives show no affinity to RBP. These results suggest that the binding site of RBP is more restrictive to the retinoyl moiety than the binding site of cellular retinoid-binding proteins and therefore tolerates less chemical modification on the hydrophobic part of the ROL molecule. Moreover, when using these derivatives as ligands 2.4 times more CRABP and 3.9 times more CRBP could be measured with the PAGE technique as compared when using the natural [3H]ligands. The CD-270 derivatives might therefore be used as stable ligands for the study of both CRBP and CRABP. Since CD-270(OH) binds to the CRBP this may lead to the development of new synthetic analogues of ROL which could be used as tools for the study of the role of CRBP in the transport and metabolism of ROL.

ISSN:1660-5527    

DOI:10.1159/000210939

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The arotinoid temarotene (Ro 15–0778) and its metabolite Ro 14–6113 were examined in a variety of in vitro assays quantitating parameters of human immune functions. Both immunosuppressive and immunostimulatory activities of these compounds were identified. These activities were compared with those of the known immunomodulatory compound ciclosporin A (CsA) at concentrations corresponding to clinically effective plasma concentrations. Like CsA, Ro 14–6113 inhibited the mitogen- or alloantigen-induced proliferation of T cells as well as their capacity to secrete interleukin-2 (IL-2), interferon-γ and tumor necrosis factor α. Ro 15–0778 showed no activity in inhibiting cytokine secretion and was considerably less effective than Ro 14–6113 in inhibiting T cell proliferation. Ro 14–6113 was more effective than CsA in inhibiting IL-2 receptor expression. Ro 14–6113 modulated both positively or negatively the proliferation of B cells, depending on the concentration. Ro 14–6113 inhibited the secretion of IgM, IgG, and IgA, while stimulating IgE secretion. A different profile of activity for Ro 14–6113 and CsA was observed, suggesting differing effectiveness in immunologically mediated diseases.

ISSN:1660-5527    

DOI:10.1159/000210940

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The effects of acitretin and etretinate on angiogenesis induced in Balb/c mice by intradermal injection of keratinocyte tumor cell lines were evaluated. It was shown that both retinoids are capable of inhibiting angiogenesis evoked by a human epidermoid carcinoma cell line (A431). Acitretin, but not etretinate, inhibited also angiogenesis induced by the spontaneously transformed murine keratinocyte cell line Pam 212 and by the established tumorigenic SKv cell line harboring the HPV16 genome. We suggest that inhibition of blood vessel formation may be one of the mechanisms responsible for the anticancerogenic effect of retinoids.

ISSN:1660-5527    

DOI:10.1159/000210941

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The concentration of 3,4-didehydroretinol, an epidermal metabolite of retinol, is changed both in association with keratinizing disorders and during treatment with certain synthetic retinoids. To delineate further the factors regulation biosynthesis of 3,4-didehy-droretinol, keratinocytes from three different layers of normal epidermis were prepared by trypsinization and incubated with [3H]-retinol for 20 h. Cell-bound [3H]-retinol and 3,4-[3H]-didehydroretinol were separated by high-performance liquid chromatography. The results indicate that the uptake of retinol and the synthesis of 3,4-didehydroretinol occur predominantly in undifferentiated cells from the basal and spinous layers of the epidermis.

ISSN:1660-5527    

DOI:10.1159/000210942

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

To investigate the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) and of interleukin-3 (IL-3) by human keratinocytes in vitro, adult human keratinocytes (aHKc) from 3 different donors and a spontaneously transformed keratinocytic line (HaCaT) were cultured and exposed to various cytokines and to the protein kinase C-activating agent phorbol-12-myristate-13-acetate (PMA). GM-CSF and IL-3 were measured by highly specific and sensitive immunoassays. Our findings showed that long-term cultured aHKc and HaCaT cells are capable of secreting GM-CSF but not IL-3 upon cytokine and PMA stimulation. Both interleukin-1 and tumor necrosis factor α, which are known to be present in human epidermis, particularly during cutaneous inflammatory processes, were found to stimulate GM-CSF release. Therefore, we conclude that increased GM-CSF levels may play an important role in the interactions between epidermal keratinocytes and blood cells in vivo.

ISSN:1660-5527    

DOI:10.1159/000210943

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Single-cell suspensions of murine and human epidermal cells were studied for the presence of peptidoleukotrienes (LTs), using in vitro guinea pig ileum contraction as bioassay and a commercial radioimmunoassay. The calcium ionophore A23187 at 5 × 10-6M alone or in combination with arachidonic acid at 10-4M caused release of LTC4/D4 within 10–30 min and for up to 18 h. LTB4, as was measured in the chemotaxis assay, was released at different levels and with different kinetics from the same cells. Epidermal cells may thus regulate cutaneous inflammation by secreting potent vasoactive and muscle-contracting in addition to chemotactic lipid mediators.

ISSN:1660-5527    

DOI:10.1159/000210944

出版商:S. Karger AG    

年代:1991

数据来源: Karger