Asunto(s)
Compensación de Dosificación (Genética) , Proteínas de Drosophila/genética , Silenciador del Gen , Células Madre/metabolismo , Animales , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Epigénesis Genética , Femenino , N-Metiltransferasa de Histona-Lisina , Histonas/química , Histonas/metabolismo , Humanos , Masculino , Modelos Genéticos , Proteína de la Leucemia Mieloide-Linfoide , Neoplasias/etiología , Nucleosomas/metabolismo , Complejo Represivo Polycomb 1 , Proteínas del Grupo Polycomb , Proto-Oncogenes/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ubiquitina/metabolismoRESUMEN
BACKGROUND: Previous studies demonstrating that the neoplastic cells in Sézary syndrome and tumor stage mycosis fungoides express interleukin 4 (IL-4), IL-5, and IL-10 have resulted in the concept that cutaneous T-cell lymphomas are derived from CD4(+) T cells with a T(H)2 type cytokine profile. OBJECTIVE: To determine the cytokine profile in CD30(-) primary cutaneous large T-cell lymphomas, which represent a subgroup of cutaneous T-cell lymphoma with an aggressive clinical behavior (5-year survival rate of 15%). DESIGN AND METHODS: Seven biopsy specimens were taken from 4 patients with CD30(-) primary cutaneous large T-cell lymphomas and studied for the expression of T(H)1 (IL-2 and interferon gamma) and T(H)2 (IL-4, IL-5, IL-10) cytokines using a reverse transcription-polymerase chain reaction technique. Skin biopsy specimens from patients with Sézary syndrome, mycosis fungoides, atopic dermatitis, or psoriasis were included as controls. RESULTS: In the 7 CD30(-) primary cutaneous large T-cell lymphomas showing an almost pure population of large tumor cells (>90%), no expression of IL-4 was found, and IL-5 was only found in 1 of 7 cases. In control biopsy specimens, expression of IL-4 and/or IL-5 was demonstrated in atopic dermatitis (3/3), tumor stage mycosis fungoides (2/2), and Sézary syndrome (3/3), but not in plaque stage mycosis fungoides. CONCLUSION: Our results demonstrate that CD30(-) primary cutaneous large T-cell lymphomas do not produce T(H)2 cytokines, illustrating that not all cutaneous T-cell lymphomas have a T(H)2 cytokine profile.
Asunto(s)
Citocinas/metabolismo , Antígeno Ki-1/metabolismo , Linfoma Cutáneo de Células T/metabolismo , ARN Mensajero/metabolismo , Neoplasias Cutáneas/metabolismo , Células Th2/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Citocinas/genética , Dermatitis Atópica/inmunología , Dermatitis Atópica/metabolismo , Dermatitis Atópica/patología , Humanos , Inmunofenotipificación , Interferón gamma/biosíntesis , Interferón gamma/genética , Interleucinas/biosíntesis , Interleucinas/genética , Linfoma Cutáneo de Células T/inmunología , Linfoma Cutáneo de Células T/patología , Masculino , Persona de Mediana Edad , Micosis Fungoide/inmunología , Micosis Fungoide/metabolismo , Micosis Fungoide/patología , Psoriasis/inmunología , Psoriasis/metabolismo , Psoriasis/patología , Síndrome de Sézary/inmunología , Síndrome de Sézary/metabolismo , Síndrome de Sézary/patología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Células TH1/inmunologíaRESUMEN
Epidermal infiltration by neoplastic CD4+ T cells is a characteristic histologic feature of early stage mycosis fungoides, the most common type of cutaneous T cell lymphoma (CTCL). The mechanisms involved in epidermotropism are unknown. It has been suggested that the CXC chemokines IL-8 and interferon-gamma inducible protein 10 (IP-10) may play a role, but evidence that these chemokines are produced within the epidermis in epidermotropic CTCL is lacking. In this study skin biopsies from 17 CTCL patients, including 12 mycosis fungoides, four pleomorphic CTCL, and one CD8+ CTCL, were investigated for epidermal IL-8 and IP-10 mRNA expression by RNA in situ hybridization. In addition, the expression of monokine induced by gamma-interferon (Mig) mRNA, a CXC chemokine closely related to IP-10, was studied as well. The expression of IL-8 receptors A and B (CXCR1 and CXCR2, respectively) was investigated by immunohistochemistry. The results were correlated with the number and phenotype of epidermotropic T cells. Epidermal expression of IP-10 and Mig mRNA was detected in 10 of 11 and seven of 11 epidermotropic CTCL, respectively, but not in five nonepidermotropic CTCL biopsies or normal human skin. Epidermal IP-10 and Mig mRNA expression correlated with epidermal infiltration of CD4+ T cells, but not of CD8+ T cells. IL-8 mRNA was demonstrated in the epidermis of only two of 15 CTCL biopsies, and was associated, in both cases, with accumulation of neutrophils. Consistently, immunostaining of the (intraepidermal) T cells with antibodies against CXCR1 and CXCR2 was not observed. In conclusion, the results of this study indicate that IP-10, and to a lesser extent Mig, but not IL-8 is involved in the preferential infiltration of neoplastic CD4+ T cells in CTCL.
Asunto(s)
Quimiocinas CXC/genética , Péptidos y Proteínas de Señalización Intercelular , Interferón gamma/farmacología , Interleucina-8/genética , Linfoma Cutáneo de Células T/metabolismo , ARN Mensajero/análisis , Neoplasias Cutáneas/metabolismo , Antígenos CD/fisiología , Quimiocina CXCL10 , Quimiocina CXCL9 , Humanos , Inmunohistoquímica , Hibridación in Situ , Receptores de Quimiocina/fisiología , Receptores de Interleucina/fisiología , Receptores de Interleucina-8A , Receptores de Interleucina-8BRESUMEN
AIMS: To investigate the expression of pepsinogen A3 (Pg3) encoding genes in the gastric mucosa of normal controls and subjects with atrophic gastritis and gastric cancer. METHODS: One hundred and fifty nine patients underwent upper gastrointestinal endoscopy with sampling of gastric biopsy specimens and serum. Pg3 isoproteins were determined by electrophoresis in serum and gastric mucosal biopsy specimens. Pg3 encoding genes were assessed by PCR in DNA obtained from peripheral blood. RESULTS: One hundred and one subjects (82 normal histology/chronic gastritis, 17 atrophic gastritis, two gastric cancer) showed a pepsinogen phenotype with presence of Pg3 and a corresponding pepsinogen genotype with presence of Pg3 encoding genes. Fifty eight subjects showed a phenotype lacking Pg3. In 39 of them (23 normal histology/chronic gastritis, 11 atrophic gastritis, five gastric cancer), a corresponding genotype without Pg3 encoding genes was found. However, in the remaining 19 subjects (4 normal histology/chronic gastritis, nine atrophic gastritis, six gastric cancer); Pg3 encoding genes were demonstrable in the absence of Pg3 production. CONCLUSIONS: Unexpressed Pg3 encoding genes can be shown in many cases of atrophic gastritis and gastric cancer, but rarely in healthy controls and subjects with superficial gastritis. The correlation of atrophic gastritis and gastric cancer with a pepsinogen phenotype lacking Pg3 can be explained by loss of expression of Pg3 encoding genes throughout the complete gastric mucosa. The mechanism of such loss and the importance as a marker for premalignant degeneration have to be elucidated.