Transforming growth factor type β (TGF β) inhibits G1 to S transition, but not activation of human B lymphocytes

Smeland, Erlend B.; Blomhoff, Heidi Kiil; Holte, Harald; Ruud, Even; Beiske, Klaus; Funderud, Steinar; Godal, Tore; Ohlsson, Rolf

doi:10.1016/0014-4827(87)90264-3

Cited by 99 publications

(47 citation statements)

References 19 publications

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“…These growth-suppressive effects, however, were only apparent after incubation periods greater than 24 h. The need for such prolonged exposure times with TGF-␤1 has previously been reported by other groups and suggests that growth inhibition could be mediated, at least in part, at the level of gene expression (4,23,54). Interestingly, TGF-␤1 did not induce a G 1 /S arrest in FDCP-Mix cells as has been observed in other cell systems (55)(56)(57), and neither was any other phase of the cell cycle specifically arrested. The observed antiproliferative effects of TGF-␤1 on FDCP-Mix cells may therefore be explained by delayed progression of cells through all phases of the cell cycle.…”

Section: Tgf-␤1-mediated Apoptosis Is Inhibited By Expression Of Bcl-supporting

confidence: 65%

Transforming Growth Factor-β1 Induces Apoptosis Independently of p53 and Selectively Reduces Expression of Bcl-2 in Multipotent Hematopoietic Cells

Francis¹,

Heyworth²,

Spooncer³

et al. 2000

Journal of Biological Chemistry

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Section: Tgf-␤1-mediated Apoptosis Is Inhibited By Expression Of Bcl-supporting

confidence: 65%

Transforming Growth Factor-β1 Induces Apoptosis Independently of p53 and Selectively Reduces Expression of Bcl-2 in Multipotent Hematopoietic Cells

Francis¹,

Heyworth²,

Spooncer³

et al. 2000

Journal of Biological Chemistry

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“…In addition, EBV-associated B-lymphoproliferations occur at increased frequency in these patients (17,18 tive when the factor is added early and that it has only minor effects on already activated cells (23 (31) and IgA secretion (32). Other cytokines, such as IL-6 are likely to also be involved in the subclass imbalance, since in transgenic mice that overexpress IL-6 in B cells, IgG I is the major contributor to the hypergammaglobulinemia (33).…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor-beta and suppression of humoral immune responses in HIV infection.

Kekow

Wachsman²,

McCutchan³

et al. 1991

J. Clin. Invest.

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We reported previously that PBMC from HIV+ patients spontaneously release increased levels of TGF#1, contributing to defects in cellular immune responses. This study defines the implications of TGF# overexpression for humoral immunity in HIV infection. We found that upon Staphylococcus aureus Cowan I (SAC) stimulation of cells from HIV+ donors, B-lymphocyte proliferative responses were decreased. This deficiency correlated closely (r = 0.7, P < 0.001) with increased TGF# secretion by PBMC from HIV-infected donors. Conditioned medium from HIV+ PBMC and purified TGF#1 had similar inhibitory effects on SAC-or EBV-induced B-cell proliferation, and B cells from HIV-infected donors were as sensitive to inhibition by TGF,B as cells from normal donors. Antibodies to TGFti1 neutralized the inhibitory effect of HIV+ culture supernatants on normal B cells and increased low proliferative responses by HIV+ cells.Using PWM as stimulus for B cell differentiation, it was shown that activated TGF, from HIV+ PBMC is able to significantly reduce the induction of immunoglobulins and this effect was also abrogated by anti-TGFj#.

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“…The effects of TGF-␤1 on human B cells have been less well characterized. TGF-␤1 pretreatment of primary B cells has been demonstrated to block activation signal-induced proliferation (11)(12)(13)(14) and to inhibit Ig secretion (15)(16)(17), and may promote class switching to an IgA phenotype (18). It has also been suggested that TGF-␤1 can induce apoptosis in human primary B lymphocytes (19 -21) and BL cell lines (20,(22)(23)(24)(25)(26).…”

mentioning

confidence: 99%

Apoptosis Induced by TGF-β1 in Burkitt’s Lymphoma Cells Is Caspase 8 Dependent But Is Death Receptor Independent

Inman

Allday

2000

The Journal of Immunology

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TGF-β is a potent inducer of apoptosis in many Burkitt’s lymphoma (BL) cell lines. In this study, we characterize this apoptotic process in the EBV-negative BL41 cell line. Induction of apoptosis was detected as early as 8 h after TGF-β treatment, as assayed by TUNEL and poly(ADP-ribose) polymerase cleavage. FACS analysis demonstrates that this proceeds predominately from the G1, but also from the G2/M phases of the cell cycle. We observed no early detectable changes in the steady-state levels of Bcl-2 and several of its family members after TGF-β treatment. We detected cleavage of caspases 2, 3, 7, 8, and 9 into their active subunits. Consistent with the involvement of these enzymes in TGF-β-mediated apoptosis, the broad spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(Ome)-flouromethylketone (ZVAD-fmk) blocked TGF-β-induced apoptosis and revealed a G1 arrest in treated cells. Use of specific caspase inhibitors revealed that the induction of apoptosis is caspase 8 dependent, but caspase 3 independent. Activation of caspase 8 has been shown to be a critical event in death receptor-mediated apoptosis. However, TGF-β treatment of BL41 cells was found not to affect the cell surface expression of Fas, TNF-R1, DR3, DR4, or DR5, or the steady-state expression levels of Fas ligand, TNF-R1, DR3, DR4, and DR5. Furthermore, blocking experiments indicated that TGF-β-mediated apoptosis is not dependent on Fas ligand, TNF-α, tumor necrosis-like apoptosis-inducing ligand, or TNF-like weak inducer of apoptosis signaling. Therefore, it appears that TGF-β induces apoptosis in BL cell lines via caspase 8 in a death receptor-independent fashion.

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Transforming growth factor type β (TGF β) inhibits G1 to S transition, but not activation of human B lymphocytes

Cited by 99 publications

References 19 publications

Transforming Growth Factor-β1 Induces Apoptosis Independently of p53 and Selectively Reduces Expression of Bcl-2 in Multipotent Hematopoietic Cells

Transforming Growth Factor-β1 Induces Apoptosis Independently of p53 and Selectively Reduces Expression of Bcl-2 in Multipotent Hematopoietic Cells

Transforming growth factor-beta and suppression of humoral immune responses in HIV infection.

Apoptosis Induced by TGF-β1 in Burkitt’s Lymphoma Cells Is Caspase 8 Dependent But Is Death Receptor Independent

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