Growth regulation of simian and human AIDS-related non-Hodgkin's lymphoma cell lines by TGF-β1 and IL-6

Ruff, Kristin; Puetter, Adriane; Lévy, Laurence

doi:10.1186/1471-2407-7-35

Cited by 9 publications

(10 citation statements)

References 51 publications

(74 reference statements)

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“…First, it has been demonstrated that many tumor cells express IL-6R, rendering them responsive to paracrine stimulation by IL-6 which the tumor clone itself generally fails to release [28]. Secondly, a further study has indicated that the sensitivity of immunoblastic HIV-related DLBCL to TGF-beta1-mediated growth inhibition may be overcome through the stimulation of proliferative and anti-apoptotic signals by IL-6, particularly the rapid activation of STAT3 [29]. Taken together, there is now preclinical data from HIV-related lymphoma as well as clinical data from both longitudinal observation and intervention with anti-IL-6 antibodies in PTLD to suggest an important role for IL-6 in both development and maintenance of malignant lymphocyte proliferation in a background of immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

IL-6 and IL-10 in post-transplant lymphoproliferative disorders development and maintenance: a longitudinal study of cytokine plasma levels and T-cell subsets in 38 patients undergoing treatment

Hinrichs¹,

Wendland²,

Zimmermann³

et al. 2011

Transplant International

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Summary IL‐6 and IL‐10 have previously been implicated in the pathogenesis of post‐transplant lymphoproliferative disorders (PTLD) and, like peripheral lymphocyte populations, are markers of immune status that are amenable to study in vivo. Thus, we analyzed cytokine plasma levels as well as lymphocyte subsets in a longitudinal analysis of 38 adult transplant recipients undergoing treatment for PTLD. Pretherapeutically, we found significantly elevated IL‐6 (13.8 pg/ml) and IL‐10 plasma levels (54.7 pg/ml) – in the case of IL‐10, even higher in treatment nonresponders than in responders (116 vs. 14 pg/ml). Over time, however, IL‐10 levels did not correlate with the course of disease, whereas those of IL‐6 did, falling in responders and rising in nonresponders. These findings were independent of histological EBV‐status, treatment type, and total peripheral T‐cell counts, which were significantly reduced in patients with PTLD. Our observations support the idea that although IL‐10 is important for creating a permissive environment for post‐transplant lymphoma development, IL‐6 is associated with PTLD proliferation. The analysis of lymphocyte subsets further identified HLA‐DR+ CD8+ lymphocyte numbers as significantly different in non‐PTLD controls (33%), treatment responders (44%) and nonresponders (70%). Although the specificity of these cells is unclear, their increase might correlate with the impaired tumor‐specific cytotoxic‐T‐lymphocyte (CTL)‐response in PTLD.

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Section: Discussionmentioning

confidence: 99%

IL-6 and IL-10 in post-transplant lymphoproliferative disorders development and maintenance: a longitudinal study of cytokine plasma levels and T-cell subsets in 38 patients undergoing treatment

Hinrichs¹,

Wendland²,

Zimmermann³

et al. 2011

Transplant International

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“…Autoimmune deficiency syndrome-derived diffuse large B-cell lymphoma cells are sensitive to growth inhibition by TGF-b; however, IL-6 production in these cells may overcome this inhibition by stimulating proliferative and antiapoptotic signals, particularly through the activation of STAT3. 80 Transgenic mouse studies suggest that IL-6 overexpression is involved in lymphoproliferative disorders, such as Castleman disease. 77 Patients may succumb to infections, or their disease may evolve to a more aggressive form.…”

Section: Preclinical Studiesmentioning

confidence: 99%

Interleukin‐6 and its receptor in cancer

Hong

Angelo

Kurzrock

2007

Cancer

342

127

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Interleukin-6 (IL-6) plays a major role in the response to injury or infection and is involved in the immune response, inflammation, and hematopoiesis. Its deregulation impacts numerous disease states, including many types of cancer. Consequently, modulating IL-6 may be an innovative therapeutic strategy in several diseases. A review of relevant published literature regarding IL-6 and its receptor was performed. In addition, a review of the relevance of this cytokine system to human illness, particularly in cancer, was undertaken. IL-6 is a pleiotropic cytokine that is involved in the physiology of virtually every organ system. Aberrant expression of this cytokine has been implicated in diverse human illnesses, most notably inflammatory and autoimmune disorders, coronary artery and neurologic disease, gestational problems, and neoplasms. In cancer, high levels of circulating IL-6 are observed in almost every type of tumor studied and predict a poor outcome.

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“…We recently characterized UMCL01-101 as immunoblastic AIDS-DLBCL (AIDS-IBL) based on expression of the EBV-encoded oncogenes LMP-1 and EBNA2 and the absence of detectable BCL-6. 46 Immunoblot analysis of total cellular protein demonstrated that 2F7 and UMCL01-101 cells express both PKCβ1 and PKCβ2. In contrast, BCBL1 cells lack PKCβ2 expression and express only PKCβ1 (Fig.…”

Section: Resultsmentioning

confidence: 96%

Protein Kinase C-Beta Inhibition Induces Apoptosis and Inhibits Cell Cycle Progression in Acquired Immunodeficiency Syndrome–Related Non-Hodgkin Lymphoma Cells

Saba

Lévy

2012

Journal of Investigative Medicine

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AIDS-related Non-Hodgkin Lymphoma (AIDS-NHL) constitutes an aggressive variety of lymphomas characterized by increased extranodal involvement, relapse rate and resistance to chemotherapy. PKCβ targeting showed promising results in preclinical and clinical studies involving a wide variety of cancers, but studies describing the role of PKCβ in AIDS-NHL are primitive if not lacking. In the present study, three AIDS-NHL cell lines were examined: 2F7 (AIDS-Burkitt Lymphoma), BCBL-1 (AIDS-Primary Effusion Lymphoma) and UMCL01-101 (AIDS-Diffuse Large B Cell Lymphoma). Immunoblot analysis demonstrated expression of PKCβ1 and PKCβ2 in 2F7 and UMCL01-101 cells, and PKCβ1 alone in BCBL-1 cells. The viability of 2F7 and BCBL-1 cells decreased significantly in the presence of PKCβ-selective inhibitor at IC50 of 14 μM and 15 μM, respectively, as measured by MTS assay. In contrast, UMCL01-101 cells were relatively resistant. As determined using flow cytometric TUNEL assay with propidium iodide staining, the responsiveness of sensitive cells was associated with apoptotic induction and cell cycle inhibition. PKCβ-selective inhibition was observed not to affect AKT phosphorylation, but to induce a rapid and sustained reduction in the phosphorylation of GSK3β, ribosomal protein S6, and mTOR in sensitive cell lines. The results indicate that PKCβ plays an important role in AIDS-related NHL survival, and suggest that PKCβ targeting should be considered in a broader spectrum of NHL. The observations in BCBL-1 were unexpected in the absence of PKCβ2 expression and implicate PKCβ1 as a regulator in those cells.

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Growth regulation of simian and human AIDS-related non-Hodgkin's lymphoma cell lines by TGF-β1 and IL-6

Cited by 9 publications

References 51 publications

IL-6 and IL-10 in post-transplant lymphoproliferative disorders development and maintenance: a longitudinal study of cytokine plasma levels and T-cell subsets in 38 patients undergoing treatment

IL-6 and IL-10 in post-transplant lymphoproliferative disorders development and maintenance: a longitudinal study of cytokine plasma levels and T-cell subsets in 38 patients undergoing treatment

Interleukin‐6 and its receptor in cancer

Protein Kinase C-Beta Inhibition Induces Apoptosis and Inhibits Cell Cycle Progression in Acquired Immunodeficiency Syndrome–Related Non-Hodgkin Lymphoma Cells

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