TY - JOUR
T1 - Spontaneous interleukin-5 production in cutaneous T-cell lymphoma lines is mediated by constitutively activated Stat3
AU - Nielsen, Mette
AU - Nissen, Mogens H
AU - Gerwien, Jens
AU - Zocca, Mai-Britt
AU - Rasmussen, Helene M
AU - Nakajima, Koichi
AU - Röpke, Carsten
AU - Geisler, Carsten
AU - Kaltoft, Keld
AU - Ødum, Niels
N1 - Keywords: Cytokines; DNA-Binding Proteins; Humans; Interleukin-13; Interleukin-5; Interleukin-6; Lymphoma, T-Cell, Cutaneous; STAT3 Transcription Factor; T-Lymphocytes; Trans-Activators; Transfection; Tumor Cells, Cultured
PY - 2002
Y1 - 2002
N2 - Mycosis fungoides is a low-grade cutaneous T-cell lymphoma (CTCL) of unknown etiology. In advanced stages of CTCL, a shift in cytokine profile from T(H)1 to T(H)2 is observed, which coincides with eosinophilia, high levels of immunoglobulin E, and increased susceptibility to bacterial infections. It is, however, unknown why T(H)2 cytokines predominate in advanced CTCL, and the cellular source of these cytokines also remains to be identified. In several leukemias and lymphomas, constitutively activated signal transducer and activator of transcription (Stat) signaling pathways have been detected. In a previous study, constitutive activation of Stat3 was found in tumor cells isolated from affected skin and blood from CTCL patients. Here, it is shown that CTCL tumor cell lines, but not nonmalignant cell lines, spontaneously produce interleukin-5 (IL-5), IL-6, and IL-13. Transfection of tumor cells with dominant-negative Stat3 almost completely blocks IL-5 production and strongly inhibits IL-13 production, whereas IL-6 production is unaffected. Thus, the data show that malignant CTCL cells themselves might contribute to the change in cytokine pattern accompanying progression of CTCL. In conclusion, constitutively activated Stat3 is found to mediate a spontaneous IL-5 production and regulate IL-13 production in CTCL cell lines, pointing toward a new role of Stat3 in malignant transformation.
AB - Mycosis fungoides is a low-grade cutaneous T-cell lymphoma (CTCL) of unknown etiology. In advanced stages of CTCL, a shift in cytokine profile from T(H)1 to T(H)2 is observed, which coincides with eosinophilia, high levels of immunoglobulin E, and increased susceptibility to bacterial infections. It is, however, unknown why T(H)2 cytokines predominate in advanced CTCL, and the cellular source of these cytokines also remains to be identified. In several leukemias and lymphomas, constitutively activated signal transducer and activator of transcription (Stat) signaling pathways have been detected. In a previous study, constitutive activation of Stat3 was found in tumor cells isolated from affected skin and blood from CTCL patients. Here, it is shown that CTCL tumor cell lines, but not nonmalignant cell lines, spontaneously produce interleukin-5 (IL-5), IL-6, and IL-13. Transfection of tumor cells with dominant-negative Stat3 almost completely blocks IL-5 production and strongly inhibits IL-13 production, whereas IL-6 production is unaffected. Thus, the data show that malignant CTCL cells themselves might contribute to the change in cytokine pattern accompanying progression of CTCL. In conclusion, constitutively activated Stat3 is found to mediate a spontaneous IL-5 production and regulate IL-13 production in CTCL cell lines, pointing toward a new role of Stat3 in malignant transformation.
M3 - Journal article
C2 - 11807001
SN - 0006-4971
VL - 99
SP - 973
EP - 977
JO - Blood
JF - Blood
IS - 3
ER -