Expression of different combinations of interleukins by human T cell leukemic cell lines that are clonally related.

Noma, Takafumi; Nakakubo, Hiroshi; Sugita, Masahiko; Kumagai, Shunichi; Maeda, Masako; Shimizu, Akira; Honjo, Tasuku

doi:10.1084/jem.169.5.1853

Cited by 60 publications

(25 citation statements)

References 18 publications

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“…There is accumulated evidence that ATL cells express IL-5 (3,41,79). Therefore, it is reasonable to speculate that the HTLV-1-encoded proteins somehow participate in the aberrant expression of IL-5.…”

Section: Discussionmentioning

confidence: 99%

“…In a study done by Murata et al, eosinophilia was detected in up to 21% of the patients suffering from ATL (36). On the other hand, a study of ATL-derived cell lines revealed that IL-5 mRNA was expressed in 50% of the ATL cell lines surveyed (41). Therefore, the aberrant increase in the level of serum IL-5 secreted from ATL cells could be speculated to the main cause of eosinophilia in ATL patients.…”

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confidence: 99%

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Triple Synergism of Human T-Lymphotropic Virus Type 1-Encoded Tax, GATA-Binding Protein, and AP-1 Is Required for Constitutive Expression of the Interleukin-5 Gene in Adult T-Cell Leukemia Cells

Yamagata

Mitani

Ueno

et al. 1997

Molecular and Cellular Biology

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Accumulated evidence demonstrates that adult T-cell leukemia (ATL) is frequently associated with eosinophilia, and human T-lymphotropic virus type 1 (HTLV-1)-infected cells frequently express interleukin-5 (IL-5).However, the molecular mechanism of constitutive IL-5 expression in HTLV-1-infected cells remains unclear. To clarify the mechanism of aberrant IL-5 expression in HTLV-1-infected cells, we investigated the response of the human IL-5 promoter to the HTLV-1-encoded protein Tax. Cotransfection experiments using Jurkat cells revealed that Tax is incapable of activating the IL-5 promoter by itself but that it synergistically transactivates the promoter with GATA-binding protein (GATA-4) and 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation. By introducing a series of mutations within the IL-5 promoter, we found that conserved lymphokine element 0 (CLE0) is responsible for mediating the signal induced by Tax-TPA. A deletion construct of the promoter indicated that the ؊75 GATA element and CLE0 are sufficient to mediate synergistic activation of the IL-5 promoter. Electrophoretic mobility shift assays using Jurkat cell nuclear extracts demonstrated that TPA induces a transcription factor to bind CLE0, and an experiment using JPX-9 cell nuclear extracts showed that Tax Human interleukin-5 (IL-5) is a cytokine produced by activated T lymphocytes and stimulates growth and differentiation of eosinophils (55). An increase in the number of eosinophils (i.e., eosinophilia) is clinically observed in patients with diseases such as idiopathic eosinophilia, asthma, Hodgkin's disease, and parasite infections. In these patients, significant levels of IL-5 in the serum or IL-5 mRNA in tissues are detected (17,29,44,54,55), and thus the high level of IL-5 expression is strongly linked to eosinophilia in a wide variety of diseases. Findings from studies of IL-5 transgenic mice have indicated the central role of IL-5 in eosinophilia (11, 37) and have shown that the high level of IL-5 expression leads to eosinophilia in vivo.Adult T-cell leukemia (ATL) is an aggressive and fatal T-cell malignancy that is caused by human T-cell lymphotropic virus type 1 (HTLV-1) infection (46,69,80). ATL is characterized by unique clinical features including rapidly developing cutaneous lesions and/or hypercalcemia (57). Eosinophilia, though not as frequently observed as the two major clinical features, is detected in patients with ATL (36,72,73,79). In a study done by Murata et al., eosinophilia was detected in up to 21% of the patients suffering from ATL (36). On the other hand, a study of ATL-derived cell lines revealed that IL-5 mRNA was expressed in 50% of the ATL cell lines surveyed (41). Therefore, the aberrant increase in the level of serum IL-5 secreted from ATL cells could be speculated to the main cause of eosinophilia in ATL patients.Tax protein is the HTLV-1-encoded protein that regulates not only HTLV-1 replication at the transcriptional level (13) but also the expression of cellular genes encoding cytokines and their recepto...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Triple Synergism of Human T-Lymphotropic Virus Type 1-Encoded Tax, GATA-Binding Protein, and AP-1 Is Required for Constitutive Expression of the Interleukin-5 Gene in Adult T-Cell Leukemia Cells

Yamagata

Mitani

Ueno

et al. 1997

Molecular and Cellular Biology

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“…The membrane-proximal, serine-rich domains of these proteins interact with Jak3 kinase and are required for cytokine mediated mitogenesis (16). In addition to IL-2, IL-6, and IL-2Ra, y, HTLV-1 infected T cells have been reported to express a multitude of other cytokines including IL-3, IL-4, IL-5, TNF-,/, and GM-CSF (8). Among them, 11L-4 was recently reported to activate T-cell proliferation by activation of Jak3 through the IL-2y chain (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells.

Xu¹,

Kang²,

Heidenreich³

et al. 1995

J. Clin. Invest.

109

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HTLV-1 infection causes an adult T cell leukemia in humans. The viral encoded protein tax, is thought to play an important role in oncogenesis. Our previous data obtained from a tax transgenic mouse model revealed that tax transforms mouse fibroblasts but not thymocytes, despite comparable levels of tax expression in both tissues. Constitutive tyrosine phosphorylation of a 130-kD protein(s) was observed in the tax transformed fibroblast B line and in HTLV-1 transformed human lymphoid lines, but not in thymocytes from Thy-tax transgenic mice. Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of Jak kinase specific antibodies, identified p130 as Jak2 in the tax transformed mouse fibroblastic cell line and Jak3 in HTLV-1 transformed human T cell lines. Phosphorylation of Jak2 in tax transformed cells resulted from high expression of IL-6. Tyrosine phosphorylation of this protein could also be induced in Balb/c3T3 cells using a supernatant from the B line, which was associated with induction of cell proliferation. Both phosphorylation and proliferation were inhibited by IL-6 neutralizing antibodies. Constitutive phosphorylation of Jak kinases may facilitate tumor growth in both HTLV-1 infected human T cells and the transgenic mouse model. (J. Clin. Invest. 1995. 96:1548-1555

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“…[5][6][7] Production of various lymphokines is also characteristic of ATL cells. These lymphokines include interleukin-1 (IL-1), [8][9][10] IL-2, 11) IL-6, 12,13) tumor necrosis factor beta (TNFβ), 14) granulocyte-macrophage colony stimulating factor, 15) tumor growth factor, 16) ATL-derived factor, 17) and parathyroid hormone-related protein.…”

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confidence: 99%

Characterization of mRNA Expression of IκBα and NF‐κB Subfamilies in Primary Adult T‐cell Leukemia Cells

Inoue

Matsuoka

Yamaguchi

et al. 1998

Japanese Journal of Cancer Research

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Tax protein of HTLV-1 activates the transcriptional capacity of the NF-κ κ κ κB family, resulting in upregulation of various genes, which are linked to phenotypic alterations of HTLV-1-infected T cells. To understand NF-κ κ κ κB regulation in HTLV-1-infected leukemic cells in vivo, we analyzed expression of NF-κ κ κ κB and Iκ κ κ κBα α α α in primary cells isolated from ATL patients. Using competitive polymerase chain reaction, we observed an elevated expression of Iκ κ κ κBα α α α mRNA in all four ATL cases tested. In contrast to the elevated mRNA levels, the levels of Iκ κ κ κBα α α α protein were remarkably reduced in some of these cases, suggesting destabilization of Iκ κ κ κBα α α α protein. On the other hand, mRNA expression of p50/p105 and p65, subfamilies of NF-κ κ κ κB, was enhanced in primary cells isolated from some ATL patients. Furthermore, the expression patterns of NF-κ κ κ κB subfamily were variable among patients and also different from those in T cells isolated from uninfected individuals. Although the number of cases analyzed was limited, we can conclude from these observations that activation of NF-κ κ κ κB is restricted to a few subfamilies in vivo. These findings in vivo are strikingly different from those in HTLV-1-infected T cell lines in vitro, in which Tax is responsible for NF-κ κ κ κB activation. It is therefore suggested that the elevation of NF-κ κ κ κB expression in leukemic cells of ATL patients might not be supported mainly by the viral protein Tax.

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Expression of different combinations of interleukins by human T cell leukemic cell lines that are clonally related.

Cited by 60 publications

References 18 publications

Triple Synergism of Human T-Lymphotropic Virus Type 1-Encoded Tax, GATA-Binding Protein, and AP-1 Is Required for Constitutive Expression of the Interleukin-5 Gene in Adult T-Cell Leukemia Cells

Triple Synergism of Human T-Lymphotropic Virus Type 1-Encoded Tax, GATA-Binding Protein, and AP-1 Is Required for Constitutive Expression of the Interleukin-5 Gene in Adult T-Cell Leukemia Cells

Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells.

Characterization of mRNA Expression of IκBα and NF‐κB Subfamilies in Primary Adult T‐cell Leukemia Cells

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