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1.
Exp Dermatol ; 9(4): 248-51, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10949545

RESUMO

Cytokines are of major importance for the pathogenesis of cutaneous T-cell lymphomas (CTCL). Recent data suggested that IL-15 and IL-16 are survival/growth factors for the malignant T cells in these entities. To investigate the expression of IL-15 and IL-16 in mycosis fungoides (MF) and CD30+ pleomorphic T-cell lymphoma in vivo, we established a competitive RT-PCR technique. Analyzing skin biopsies from CTCL patients at different stages in comparison to psoriatic and healthy skin, we found IL-15 and IL-16 mRNA overexpression in both CTCL entities. Remarkably, there was some evidence for a stage-dependent increase during MF progression. We found only slight overexpression in early stage MF, when only few tumor cells are detectable within the infiltrates, whereas marked overexpression was found in more advanced lesions, which are characterized by a higher density of malignant cells. These results suggested that CTCL cells themselves might produce the cytokines. To further elucidate this hypothesis, two CTCL cell lines were analyzed but gave conflicting results. Therefore, the cellular origin of the IL-15 and IL-16 overexpression in CTCL remains unclear. Considering the significant overexpression of IL-15 and IL-16 and their biological capacities it is likely that these cytokines contribute to the tumor development. So, they might be involved in growth and skin homing of CTCL cells.


Assuntos
Interleucina-15/metabolismo , Interleucina-16/metabolismo , Linfoma Cutâneo de Células T/imunologia , Neoplasias Cutâneas/imunologia , Adulto , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA/genética , Expressão Gênica , Humanos , Interleucina-15/genética , Interleucina-16/genética , Antígeno Ki-1/metabolismo , Linfoma Cutâneo de Células T/etiologia , Linfoma Cutâneo de Células T/patologia , Micose Fungoide/imunologia , Psoríase/imunologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia
2.
Arch Dermatol Res ; 292(4): 164-72, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10836609

RESUMO

IL-10 is a promising candidate for the treatment of cutaneous disorders. Antipsoriatic efficacy of systemic IL-10 treatment has been already demonstrated. This includes histomorphological changes in the epidermis, suggesting effects on keratinocytes. However, less is known about direct effects of IL-10 on this cell population, although effects are likely since IL-10 receptor expression on keratinocytes has been demonstrated recently. Therefore we analysed the effects of IL-10 on keratinocytes in vitro, using concentrations of human recombinant IL-10 corresponding to those detectable in plasma during therapy. Proliferation, cytokine formation (IL-6, IL-8, IL-1ra), and expression of surface molecules (MHC class I and II, costimulatory molecules CD80 and CD86, CD29, CD54, CD95) were measured in stimulated and unstimulated cells. Although stimulation influenced the expression levels of certain surface markers, no or only slight effects of IL-10 were found. In contrast considerable inhibitory effects of IL-10 on surface molecule expression and cytokine secretion by peripheral blood human monocytes were observed. Our results suggest that the antipsoriatic activity of IL-10 is rather caused by modulatory effects on circulating immune cells, which subsequently might infiltrate the skin, than by direct effects on human keratinocytes. Considering the remarkable antipsoriatic activity of IL-10 and the observation that IL-10 seem to act on peripheral blood mononuclear cells but not on keratinocytes provide further evidence that circulating immune cells play a key role in the pathology of psoriasis. Finally, our results argue against the value of IL-10 therapy in dermatoses strictly limited to keratinocyte involvement.


Assuntos
Interleucina-10/farmacologia , Queratinócitos/efeitos dos fármacos , Antígenos CD/análise , Antígeno B7-1/análise , Antígeno B7-2 , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/análise , Relação Dose-Resposta a Droga , Antígenos HLA/análise , Humanos , Integrina beta1/análise , Molécula 1 de Adesão Intercelular/análise , Queratinócitos/imunologia , Glicoproteínas de Membrana/análise , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Psoríase/sangue , Psoríase/tratamento farmacológico , Psoríase/imunologia , Proteínas Recombinantes/farmacologia
3.
Exp Dermatol ; 9(1): 71-6, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10688378

RESUMO

Physiologically, B-lymphocytes are not present in the skin. Even in pathological situations they rarely occur. In contrast, primary cutaneous B-cell lymphomas (CBCL) are characterized by proliferation of B lymphocytes within the skin. This suggests the existence of a certain microenvironment supporting homing and expansion of clonal B cells. Cytokines were demonstrated to be involved in the pathogenesis of cutaneous lymphomas of T-cell origin. Cytokine expression in cutaneous B-cell lymphoma lesions, however, has not been investigated so far. Therefore, the mRNA level of several cytokines was analyzed in biopsies from 7 patients with CBCL and compared to pleomorphic T-cell lymphoma (n = 6), psoriasis (n = 9), and healthy skin (n = 7), using a competitive RT-PCR approach. An overexpression of TNF-alpha, IL-10, and IL-6 was found. Enhanced IL-8 mRNA expression was detected in 2/7 cases. The overexpression of IL-6 and IL-10 in CBCL might be of particular importance, since these cytokines are considered to support B-cell growth. Additionally, the overexpression of IL-10 may contribute to tumor progression since this immunosuppressive cytokine might be involved in downregulation of immunological tumor surveillance, in part by inhibiting type 1 cytokine formation. In fact, we did not detect IFN-gamma and IL-2 expression. Taken together, we found a cytokine pattern in CBCL lesions which might contribute to tumor B-cell growth.


Assuntos
Citocinas/genética , Linfoma de Células B/imunologia , Neoplasias Cutâneas/imunologia , Adulto , Expressão Gênica , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Interleucina-10/genética , Interleucina-6/genética , Interleucina-8/genética , Linfoma de Células B/genética , Linfoma de Células B/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Fator de Necrose Tumoral alfa/genética
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