Interleukin-6 functions as an intracellular growth factor in hairy cell leukemia in vitro.

Barut, Bruce A.; Chauhan, Dharminder; Uchiyama, Hiroshi; Anderson, Kenneth C.

doi:10.1172/jci116839

Cited by 44 publications

(13 citation statements)

References 57 publications

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“…IL-6 exerts its effects by binding to a high-affinity receptor complex consisting of two subunits: a low-affinity 80-kD component (IL-6R) and a signal-transducing unit (gp130) that binds a complex formed by IL-6 and the soluble form of IL-6 receptor (sIL-6R); sIL-6R can be generated by shedding of the membrane-bound receptor or by IL-6R alternative mRNA splicing [2]. In accordance with its pleiotropic functions, IL-6 has been reported both to exert anti-inflammatory effects in local and systemic acute inflammatory responses by controlling the levels of proinflammatory cytokines [3, 4]and to play a role in the pathogenesis of several disorders including autoimmune diseases [5], lymphoid malignancies [6], and different kinds of inflammatory states [7]. In particular, IL-6 has been implicated as an important mediator of progression in immune system mediated renal diseases, such as mesangiocapillary glomerulonephritis or lupus nephritis, where it is considered an autocrine growth factor for mesangial cells [8].…”

Section: Introductionmentioning

confidence: 99%

Selective Induction of MCP-1 in Human Mesangial Cells by the IL-6/sIL-6R Complex

Coletta

Soldo

Polentarutti

et al. 2000

Nephron Exp Nephrol

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Interleukin (IL) 6, an autocrine growth factor for mesangial cells, and chemokines, which are released from activated mesangial cells and induce leukocyte infiltration, play a critical role in the progression of immune system mediated renal diseases. Since the reciprocal relationship between IL-6 and chemokines in renal inflammation has been barely investigated, we have analyzed whether IL-6 (500 ng/ml), alone or in combination with the soluble form of its receptor (sIL-6R, 200 ng/ml), can induce normal human mesangial cells (NHMC) to release alpha and/or beta chemokines: MCP-1 (monocyte chemoattractant protein 1), IL-8, Rantes (regulated on activation, normal T cell expressed and secreted), and MIP-1α (macrophage inflammatory protein 1α). Whereas IL-6 or sIL-6R alone were ineffective in inducing significant chemokine release from NHMC, the simultaneous treatment with IL-6 and sIL-6R showed a significant interaction, leading to a strong synergic effect on MCP-1 synthesis and release without exerting any relevant activity on IL-8, Rantes, or MIP-1α. Consistently with the unresponsiveness to IL-6, mRNA and protein expression analysis of the two subunits which form the functional IL-6 receptor showed that NHMC express only the gp130 signal-transducing chain and not the subunit-specific IL-6R (gp80). These findings support an unexpected role of the IL-6 system in kidney inflammatory reactions through the selective regulation of monocyte recruitment.

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Section: Introductionmentioning

confidence: 99%

Selective Induction of MCP-1 in Human Mesangial Cells by the IL-6/sIL-6R Complex

Coletta

Soldo

Polentarutti

et al. 2000

Nephron Exp Nephrol

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“…Recent in vitro studies suggest a novel effect of IL-6 in growth regulation of various tumor cell lines (2)(3)(4)(5)(6)(7). Multiple myeloma and AIDS-related Kaposi sarcoma-derived cells have been shown to produce IL-6 and to respond to it with proliferative activity (3,4).…”

mentioning

confidence: 99%

“…Multiple myeloma and AIDS-related Kaposi sarcoma-derived cells have been shown to produce IL-6 and to respond to it with proliferative activity (3,4). Barut et al (5) and Levy et al (6) reported that the growth-promoting role of IL-6 in tumor necrosis factorstimulated or fetal calf serum (FCS)-stimulated hairy cell leukemia or myeloma cells is due to the action of intracellular IL-6. Moreover, Lu et al (7) demonstrated that IL-6 undergoes transition from a paracrine growth inhibitor to an intracellular autocrine stimulator during progression of human melanoma.…”

mentioning

confidence: 99%

Intracellular interleukin 6 mediates platelet-derived growth factor-induced proliferation of nontransformed cells.

Roth

Nauck

Tamm

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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The functional relevance of interleukin 6 (IL-6) in platelet-derived growth factor (PDGF)-induced cell growth was evaluated in cultures of human fibroblasts, vascular smooth muscle cells, and mesangial cells. The three isoforms of the PDGF--namely, PDGF-AA, -AB, and -BB--induced the expression of the IL-6 gene and proliferation of the nontransformed cells. PDGF-induced transcription, translation, and secretion of IL-6 were diminished in the presence of IL-6 antisense oligonucleotides. While neutralizing anti-IL-6 antibodies failed to affect the growth factor-dependent cell proliferation, IL-6 antisense oligonucleotides inhibited cell division. In addition, IL-6 antisense oligonucleotides abolished PDGF-induced transcription of the genes coding for the cell division cycle 2-related protein (CDC2) and proliferating cell nuclear antigen (PCNA), both of which are regulated in a cell cycle-dependent manner. It is concluded that PDGF-dependent proliferation of nontransformed cells involves the action of intracellular IL-6.

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“…This negative result would obviously require con®rmation by other means, and tools for blocking either the activity or the synthesis of the inhibin receptor would be of interest. Taking them at face value, our observations rather suggest that inhibin acts in an autocrine manner, possibly via an intracrine loop, as do a number of other growth controlling agents, including granulocyte macrophage colony stimulating factor and erythropoietin (Pech et al, 1993), interleukine 3 (Dunbar et al, 1989), interleukine 6 (Barut et al, 1993) and platelet derived growth factor (Keating and Williams, 1988). …”

Section: Discussionmentioning

confidence: 72%

A role of inhibin as a tumor suppressor in Sertoli cells: down-regulation upon aging and repression by a viral oncogene

et al. 1999

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Inhibin, a member of the TGF-b superfamily, is synthesized in the testis by Sertoli cells and exerts an endocrine regulatory function on pituitary hormone synthesis. A distinct local function has been proposed, negatively controlling cellular growth in the testis (tumor suppressor activity). A critical test for the identi®cation of a tumor suppressor is the reversal of transformed growth properties upon re-expression of the gene in tumor-derived cell lines. Sertoli cell-derived tumoral lines were previously established from tumors that develop in elderly transgenic males which express in the testis the large T antigen of polyoma virus. Both the tumors and the cells in culture exhibited reduced levels of the inhibin a subunit mRNA. Stable transfectants were generated, in which this subunit was expressed from a heterologous promoter. All of them exhibited a strict inhibition of growth at con¯uency. On the other hand, in addition to an aging-related decrease in inhibin synthesis, the a subunit gene was down regulated in vivo in cells expressing the viral protein. The conjunction of these two factors accounts for the age-related occurrence of testicular cancers in the transgenic model, again pointing to inhibin as a potent cell growth regulator in the seminiferous epithelium.

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Interleukin-6 functions as an intracellular growth factor in hairy cell leukemia in vitro.

Abstract: The role of interleukin-6 (IL-6) in the growth of B cell derived hairy cell leukemia (HCL) was characterized.

Cited by 44 publications

References 57 publications

Selective Induction of MCP-1 in Human Mesangial Cells by the IL-6/sIL-6R Complex

Selective Induction of MCP-1 in Human Mesangial Cells by the IL-6/sIL-6R Complex

Intracellular interleukin 6 mediates platelet-derived growth factor-induced proliferation of nontransformed cells.

A role of inhibin as a tumor suppressor in Sertoli cells: down-regulation upon aging and repression by a viral oncogene

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