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P A Bécherel

Publications and source records attributed to P A Bécherel.

At least 19 recordsLinked to original sources
PubMed2001

Erythrodermic cutaneous T-cell lymphoma with disseminated pustulosis. Production of high levels of interleukin-8 by tumour cells.

Interleukin (IL) -8 is a neutrophil chemoattractant cytokine with proinflammatory and growth-promoting activities, which is involved in the pathogenesis of several inflammatory diseases. It is found in high amounts in lesional biopsies of pustular diseases such as psoriasis and palmoplantar pustulosis. We report a 50-year-old woman with a 10-year history of erythroderma with disseminated pustulosis. Skin biopsies showed an epidermotropic infiltrate composed of atypical CD4+ CD8+ lymphocytes with numerous admixed neutrophils. Peripheral blood flow cytometric analysis revealed a major clonal subset of CD3+ CD4+ CD8+ T-cell receptor Vbeta22+ atypical lymphocytes. Bone marrow biopsy, lymph node biopsy and computed thoracoabdominal tomography were normal. Serologies for human T-cell lymphotropic virus type I and human immunodeficiency virus were negative. Our patient's status deteriorated despite topical (nitrogen mustard, psoralen plus ultraviolet A) and systemic (interferon, methotrexate, multiagent chemotherapy) treatments, and she finally died. We showed that our patient's peripheral blood lymphocytes (PBL) spontaneously produced high amounts of IL-8. In contrast, PBL of patients with classical Sézary syndrome produced lower amounts of IL-8. The production of IL-8 by tumour T cells could explain this unusual clinical and histopathological presentation of cutaneous T-cell lymphoma as disseminated pustulosis.

Dermatitis, Exfoliative↗
PubMed2001

["Idiopathic" white atrophy].

INTRODUCTION: Livedoid vasculitis is a clinico-pathological entity which may be idiopathic or secondary to various disorders. The aim of this study was to search for a thrombogenic biological abnormality in patients with apparently idiopathic livedoid vasculitis. PATIENTS AND METHODS: All the patients with histologically confirmed and apparently idiopathic livedoid vasculitis were evaluated. Blood study included search for anticardiolipin, anti-anionic phospholipids and anti-beta 2 glycoprotein 1 antibodies, platelet aggregation and fibrinolytic system tests, cryofibrinogen and homocysteine serum level and factor V Q506 mutation and prothrombin 20210 G/A variant investigation. Clinical data and effects of treatments were reviewed retrospectively. RESULTS: Eleven of the 21 patients with livedoid vasculitis had an apparently idiopathic form. Seven of them (64 p. 100) had a thrombophilic state: antiphospholipid antibodies (n = 3), increased platelet aggregation (n = 1), cryofibrinogen (n = 1), decreased antithrombin III activity (n = 1) and factor V mutation (n = 1). The necrotic lesions were always localized on the lower limbs with a sensitive neuropathy in 2 cases. Complete remission was sometimes obtained with antiaggregant or anticoagulant therapy, but was unrelated to the thrombophilic abnormalities. CONCLUSION: Various thrombophilic abnormalities are frequently observed in livedoid vasculitis which seems to be the clinical expression of a thrombotic process of the microcirculation of the skin and sometimes of the peripheral nerves. The idiopathic feature of numerous cases gives evidence for the lack of our knowledge on thrombosis of the microcirculation.

Adult↗
PubMed1998

Tripe palms associated with systemic mastocytosis: the role of transforming growth factor-alpha and efficacy of interferon-alfa.

Tripe palms are thickened, moss-like or velvety textured exaggerations of the normal dermatoglyphics. The disease belongs to the spectrum of papulosquamous paraneoplastic syndromes. Although suspected, the role of transforming growth factor-alpha (TGF-alpha) has not been clearly established. A 54-year-old man with systemic mastocytosis presented with thickening and darkening of the palms and soles. We performed skin biopsies for light microscopy (including toluidine blue), in situ hybridization and double labelling, and determination of serum tryptase, histamine and TGF-alpha levels. Toluidine blue stained the mast cells that had massively infiltrated the dermis. Tripe palm samples showed extensive hyperkeratosis. The TGF-alpha probe reacted strongly with the mast cells that also reacted with the antitryptase monoclonal antibody. Elevated tryptase, histamine and TGF-alpha levels prior to interferon-alfa administration decreased under treatment. The demonstration of TGF-alpha in infiltrating mast cells, the clinical regression of tripe palms and the lowering of the serum level and the mast cell molecular signal of the cytokine when systemic mastocytosis was controlled by interferon-alfa, suggest a key role for TGF-alpha in this cutaneous paraneoplastic syndrome.

Dermatoglyphics↗
PubMed1997

Induction of IL-10 synthesis by human keratinocytes through CD23 ligation: a cyclic adenosine 3',5'-monophosphate-dependent mechanism.

Ligation of the low affinity receptor for IgE, CD23/Fc epsilonRII, in human keratinocytes (HK) and monocytes induces the synthesis of proinflammatory cytokines (IL-6 and TNF-alpha), partly under the dependence of cAMP and nitric oxide pathways. Moreover, CD23 ligation induces IL-10 production in human monocytes. Since synthesis of IL-10 by HK is still a matter of debate, we investigate whether keratinocytes could produce IL-10 upon CD23 stimulation. Here, our data show that CD23 ligation induces significant IL-10 synthesis in HK, a phenomenon inhibited by cAMP antagonists, but not by inhibitors of the nitric oxide pathway. Accordingly, cAMP agonist induced significant IL-10 synthesis by HK, while nitric oxide-releasing chemical did not. Treatment of HK with anti-IL-10 mAb potentiated their CD23-mediated TNF-alpha synthesis. These data indicate that engagement of surface CD23 on human keratinocytes induces the synthesis of IL-10, which, in turn, down-regulates their proinflammatory response.

Adjuvants, Immunologic↗
PubMed1997

Interleukin-10 and interleukin-4 inhibit intracellular killing of Leishmania infantum and Leishmania major by human macrophages by decreasing nitric oxide generation.

The host response to Leishmania infection is regulated by a specific pattern of local cytokine production. We investigated the effect of interleukin (IL)-10 and IL-4 on the leishmanicidal activity of human macrophages (M phi). As with L. major, intracellular killing of L. infantum by human M phi was obtained following ligation of surface CD23 or cell treatment with interferon-gamma (IFN-gamma). This leishmanicidal activity required nitric oxide (NO) generation by activated M phi, and it was partially mimicked by cell treatment with chemical NO donors. Addition of recombinant human IL-10 or IL-4 to CD23 mAb or IFN-gamma decreased L. infantum and L. major killing by infected M phi. IL-10 was more potent than IL-4 in inhibiting the leishmanicidal activity of human M phi. Inhibition of Leishmania killing by IL-4 and IL-10 correlated with decreased NO generation from M phi, and was reversed when exogenous NO was added to cell cultures. Therefore, IL-10 and IL-4 down-regulate leishmanicidal activity of human M phi, in part by inhibiting NO generation by these cells.

Animals↗
PubMed1997

Inducible nitric oxide synthase and proinflammatory cytokine expression by human keratinocytes during acute urticaria.

BACKGROUND: IgE/allergen-dependent activation of skin mast cells is involved in acute urticaria and leads to their IL-4 release. Previously we have demonstrated in vitro the induction of the low-affinity receptor for IgE (CD23/Fc epsilon RII) in human keratinocytes (HK) upon stimulation with IL-4. In addition, we have observed that ligation of CD23 on keratinocytes induced type II nitric oxide synthase (iNOS), leading to the release of nitric oxide (NO) and proinflammatory cytokines (TNF-alpha, IL-6). According to these in vitro data, we explored whether keratinocytes could also express iNOS, TNF-alpha, IL-6, and CD23 in acute urticaria, an in vivo model in which activation of mast cells by IgE/allergen immune complexes is involved. MATERIALS AND METHODS: INOS, TNF-alpha, IL-6, and CD23 expression by keratinocytes was studied in acute urticaria (n = 11) in biopsies from lesional and autologous normal skin by immunohistochemistry, in situ hybridization, or RT-PCR. Nitrites and TNF-alpha synthesis were assayed in supernatants of cultured lesional keratinocytes. RESULTS: INOS mRNA expression was demonstrated with RT-PCR in 10 biopsies out of 11 sections of acute urticaria lesional skin. Immunohistochemistry showed that this iNOS positivity originated from keratinocytes located close to the dermoepidermal junction; TNF-alpha and IL-6 mRNA transcription was observed in all but one iNOS+ biopsy. Immunostaining and in situ hybridization with CD23-specific probes were strong in all but one iNOS+ skin biopsy. Noninflamed autologous skin was negative for iNOS (except for a weak positivity in one case), cytokines, and CD23. CONCLUSION: The colocalization of iNOS, proinflammatory cytokines, and CD23 within keratinocytes in acute urticaria demonstrates that these cells play an important role in the initiation and maintenance of the inflammatory reaction during this disease in humans through activation of the iNOS pathway by CD23 ligation with IgE/allergen immune complexes.

Acute Disease↗
PubMed1996

CD23-mediated nitric oxide synthase pathway induction in human keratinocytes is inhibited by retinoic acid derivatives.

Retinoids exert various functions including anti-proliferative and anti-inflammatory effects on many cell types including keratinocytes and are widely used in skin diseases, such as psoriasis and acne. We have previously shown that human keratinocytes express low affinity immunoglobulin E receptor (FcepsilonRII/CD23) when stimulated with interleukin-4. Immunoglobulin E ligates CD23 and induces the production of nitrites (reflecting the mobilization of the nitric oxide [NO]-pathway) and tumor necrosis factor-alpha by human keratinocytes. Here, 13-cis and all-trans retinoic acid (RA) were shown to reduce the production of nitrites by immunoglobulin E-activated keratinocytes by 80% in a time- and concentration-dependent fashion. As a consequence, RA derivatives also reduced the production of tumor necrosis factor alpha by these cells by 70%. The level of inducible NO synthase activity in activated human keratinocytes was significantly decreased upon treatment of the cells with RA derivatives (inhibition by 60% of the mean inducible NO synthase activity with 13-cis RA, 2 microM). Treatment for 24 h with RA derivatives almost completely abolished transcription of inducible NO synthase-specific mRNA in activated keratinocytes. Therefore, RA derivatives downregulate tumor necrosis factor-alpha release and the NO-transduction pathway through the inhibition of inducible NO synthase transcription. Together, our data provide evidence for inhibition of the NO-pathway by 13-cis and all-trans retinoic acid on CD23-activated human keratinocytes. These data may clarify the mechanism of the anti-inflammatory activity of RA derivatives in skin diseases.

Cell Division↗
PubMed1995

Involvement of cyclic nucleotides in the immunomodulatory effects of nitric oxide on murine mast cells.

Nitric oxide (NO) is synthesized by various cells involved in inflammatory reactions and may then act on mast cells. In the present work, we attempted to clarify the role of this molecule on the proliferation and IgE-mediated activation of mouse bone-marrow-derived mast cells obtained by culture in the presence of IL-3 (BMMC). Treatment of BMMC with increasing concentrations of sodium nitroprusside (SNP) induced a dose-dependent inhibition of 3H-thymidine incorporation (IC50 = 50 microM) without affecting cell survival under 100 microM. Furthermore, nitric oxide dramatically decreased beta-hexosaminidase and TNF-alpha release induced by Fc epsilon RI ligation on BMMC (respectively 45 and 57% for 100 microM). These inhibitory effects are mediated at least in part through enhancement of intracellular cyclic nucleotides levels since: 1) intracellular cGMP and cAMP levels increased within minutes after NO treatment, 2) treatment of BMMC with a cAMP analogue induced antiproliferative effect on BMMC and 3) pretreatment of BMMC with a cAMP antagonist partly reversed the inhibitory activity of SNP.

Animals↗
PubMed1995

Interleukin-10 inhibits IgE-mediated nitric oxide synthase induction and cytokine synthesis in normal human keratinocytes.

Human keratinocytes (HK) generate nitric oxide (NO) and proinflammatory mediators following activation with either IgE/anti-IgE immune complexes or a combination of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Recently, interleukin-10 (IL-10) has been shown to down-regulate various inflammatory responses and to be secreted by lymphocytes and dendritic cells during skin inflammatory reactions. We show here that IL-10 down-regulates the production of tumor necrosis factor (TNF)-alpha and IL-6 by activated HK. Also, induction of inducible nitric oxide synthase (iNOS) expression in HK by IgE/anti-IgE or LPS/IFN-gamma is significantly reduced by the addition of IL-10. This effect is dose dependent and correlates with reduction of iNOS mRNA production and enzyme level. Therefore, IL-10 down-regulates NO-mediated HK inflammatory responses and may thus participate in the regulation of the skin immune network.

Antibodies, Anti-Idiotypic↗