摘要:

There is good evidence that some vascular effects of inflammation in the skin are neurogenic and involve axon reflexes in the terminal arborizations of C-fibres containing substance P, neurokinin A and calcitonin gene-related peptide (CGRP). Substance P produces dose-related wheal and flare reactions in human skin. Neurokinin A induces wheal but little or no flare and is less potent than substance P. CGRP induces both wheal and flare but is also less potent than substance P. In addition, CGRP induces a slow-onset, intense vasodilatation in human skin which persists for several hours and is associated with leucocyte infiltration: a response which is not seen with substance P. Substance P also releases histamine from mast cells in the skin and the presence or absence of a role for histamine and mast cells in neurogenic inflammation in skin is discussed.

ISSN:1660-5527    

DOI:10.1159/000210752

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

This study deals with the mechanism of the inhibitory effect exerted by the immunosuppressant ciclosporin (CsA) on phorbol-ester-induced inflammation, epidermal hyperplasia and tumor promotion in mouse skin in vivo. This effect coincides with an inhibition of the phosphorylation of a 100-kilodalton protein (p 100) in epidermal cytosol in vitro, which has been identified as elongation factor 2 (EF-2) of protein biosynthesis. Phosphorylation of EF-2 is dependent on Ca2+ and calmodulin, and inhibition of EF-2 phosphorylation by CsA is due to an interaction of CsA with calmodulin. The EF-2 phosphorylation system has a metabolic half-life of 1.5 h probably due to a rather rapid turnover rate of the EF-2 kinase. Since CsA inhibits specifically 12–0-tetradecanoylphorbol-13-acetate (TPA)-stimulated but not basal protein synthesis in epidermis, it is proposed that Ca2+/calmodulin-dependent phosphorylation of EF-2 is involved in the induction of the hyperplastic response by TPA and that CsA suppresses TPA effects by inhibition of EF-2-phosphorylation and perhaps other calmodulin-dependent processes. The potential applicability of calmodulin inhibitors in the treatment of hyperproliferative skin diseases is discussed.

ISSN:1660-5527    

DOI:10.1159/000210753

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

15-Hydroxyeicosatetraenoic acid (15-HETE), a 15-lipoxygenase (15-LO) product of arachidonic acid has the potential to inhibit leukotriene formation. In the present study the effect of 15-HETE on leukotriene B4 (LTB4)-induced polymorphonuclear leukocytes (PMN) and monocyte chemotaxis was investigated. LTB4-induced chemotaxis of PMNs was inhibited in a dose-dependent manner by 15-HETE. Maximum inhibition (68%) occurred at a 15-HETE concentration of 10-4M. The 15-LO product of eicosapentaenoic acid (15-HEPE) was approximately 10 times less potent in inhibiting LTB4-induced PMN chemotaxis. LTB4-induced chemotaxis of monocytes was unaffected by both 15-HETE and 15-HEPE. Using N-formyl-methionyl-leucyl-phenylalanine (FMLP) and complement split product C5a as chemoattractants, 15-HETE did not decrease PMN chemotaxis. Furthermore, 15-HETE itself did not affect random migration of leukocytes. The present results demonstrate that 15-HETE inhibits LTB4-induced chemotaxis of PMNs in vitro in a specific and selective way. Because 15-HETE not only inhibits formation, but also the effect of LTB4, it may be important in regulating LTB4-induced inflammation.

ISSN:1660-5527    

DOI:10.1159/000210754

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

A 5-lipoxygenase inhibitor (5-LPI) and a platelet-activating factor antagonist (PAF-A) were studied in dinitrofluorobenzene (DNFB)-induced allergic and croton-oil-induced irritant murine contact dermatitis. Both inhibitors, at 1 and 5% concentrations, significantly reduced the ear swelling in allergic dermatitis while irritant dermatitis was far less affected. This suggests that 5-lipoxygenase-dependent mediators and PAF are involved in allergic contact dermatitis and that these mediators play only a minor role in irritant dermatitis.

ISSN:1660-5527    

DOI:10.1159/000210755

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

β-Adrenergic receptor hyporesponsiveness has been observed in psoriasis and after exposure of epidermis to phorbol esters. It was the purpose of our studies to determine if forskolin, which is known to act synergistically with receptor agonists in elevating endogenous levels of cyclic AMP, could return these responses to those seen under control conditions. It was observed that topical application of phorbol ester to mouse ears in vivo led to a significant reduction in isoproterenol stimulation of cyclic AMP in vitro. Low doses of forskolin (10-7M) were able to enhance isoproterenol’s effect under these conditions. Similarly, human keratinocyte cell cultures treated with phorbol esters and human psoriatic epidermis in vitro were both hyporesponsive to isoproterenol. Again, pretreatment of these samples with forskolin restored the β-agonist stimulation to control values. These data indicate that forskolin is still able to act synergistically with β-agonists in hyporesponsive systems and suggest that forskolin may be a useful probe in defining the mechanism of this decreased responsiveness both in phorbol-ester-treated skin and in psoriasis.

ISSN:1660-5527    

DOI:10.1159/000210756

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Radical reactions of anthralin and its metabolites with skin have been studied by ESR spectroscopy. The influence of compounds which are known to suppress inflammation are described. The ESR spectra recorded during the reaction of anthralin with skin were essentially composed of one broad line centered at g = 2.0030. Similar but much weaker spectra were recorded with the dimer and no signal at all was obtained with 9, 10-dihy-droxyanthraquinone. The ESR response obtained with anthralin was neither affected by the radical scavengers 2-tert-butyl-4-methoxy-phenol (BHA), 2,6-di-tert-butyl-4-methyl-phenol (BHT) dl-α-tocopherol, nor by the antiinflammatory agents clobetasol-17-propionate or indomethacin, nor by potassium hydroxide. We infer that anthralin inflammation is not associated with the presence of anthralin-derived radicals in the skin.

ISSN:1660-5527    

DOI:10.1159/000210757

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Retinoic acid and some selected analogs were tested to evaluate their effect on skin morphogenesis and toxicity in the chick embryo. Retinoids dissolved in dimethyl sulfoxide were injected at doses varying from 10 pmol to 10 μmol into the amniotic cavity of 10-day-old chick embryos (n = 20). At 16 days of incubation, the eggs were opened to record the number of dead embryos and the number of embryos presenting club-shaped feathers. A lethal embryotoxic dose (LED50d16) which, at 16 days of incubation, provokes the death of 50% of the embryos and an effective dose (ED50) which induces production of club-shaped feathers in 50% of surviving embryos were then calculated using log-probit analysis. Retinoids could be classified according to their ED50. For example, arotinoid Ro 13–7410 appears approximatly 1,000 times more active than all transretinoic acid. However, the analogs which are more active are also more toxic. The assay described in the present study appears to be a simple and useful model for the screening of retinoids.

ISSN:1660-5527    

DOI:10.1159/000210758

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

In this study, we employed a high-frequency ultrasound system to measure the epidermal thicknesses of psoriasis plaques and normal skin in vivo. Eighty-four percent of the ultrasound measurements fell within the range of epidermal thickness determined by histology. The average thickness of untreated psoriasis measured by ultrasound was significantly greater than that of either treated psoriasis or normal skin. Ultrasound measurement of thickness was consistent with clinical assessment. Ultrasound measurements also demonstrated known variations in epidermal thickness by body site. Further development is needed to obtain measurements that are fully representative of the epidermis.

ISSN:1660-5527    

DOI:10.1159/000210760

出版商:S. Karger AG    

年代:1988

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000210762

出版商:S. Karger AG    

年代:1988

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000210765

出版商:S. Karger AG    

年代:1988

数据来源: Karger