Interleukin-1 accelerates autocrine growth of myeloma cells through interleukin-6 in human myeloma

Kawano, Masanori; Tanaka, Hitomi; Ishikawa, Hideaki; Nobuyoshi, M; Iwato, K; Asaoku, Hideki; Takahashi, Osamu; Kuramoto, A

doi:10.1182/blood.v73.8.2145.bloodjournal7382145

Cited by 10 publications

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“…These results are in agreement with previous studies reporting the presence of IL‐1β mRNA and the production of IL‐1β in cultures of bone marrow cells in MM patients ( Kawano et al , 1989a ; Cozzolino et al , 1989 ; Carter et al , 1990 ). The present in situ analysis helped to clarify conflicting reports claiming that IL‐1β was produced by either myeloma cells ( Donovan et al , 1998 ; Kawano et al , 1989a ; Cozzolino et al , 1989 ) or non‐tumoural cells ( Borset et al , 1993 ). We identified that bone‐marrow myelomonocytoid and megakaryocytic cells are IL‐1β producers together with myeloma cells.…”

Section: Discussionsupporting

confidence: 93%

“…IL‐1, mainly IL‐1β, is a potent inducer of IL‐6 production by monocytes, stromal cells and polymorphonuclear leucocytes ( Dinarello, 1996; Tosato & Jones, 1990; Marucha et al , 1991 ). This cytokine has been shown to contribute to the high IL‐6 production in the myelomatous tumoural environment ( Kawano et al , 1989a ; Cozzolino et al , 1989 ; Carter et al , 1990 ). Regarding the IL‐1 producers, controversial results have been reported.…”

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confidence: 99%

“…Regarding the IL‐1 producers, controversial results have been reported. Several groups have regarded myeloma cells as major IL‐1 producers ( Donovan et al , 1998 ; Kawano et al , 1989a ; Cozzolino et al , 1989 ) whereas others have reported that purified myeloma cells failed to express the IL‐1 gene ( Borset et al , 1993 ).…”

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confidence: 99%

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Interleukin‐1 in multiple myeloma: producer cells and their role in the control of IL‐6 production

et al. 1998

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Summary.We studied the role of interleukin (IL)-1b in patients with multiple myeloma. By in situ hybridization and immunochemistry, myeloid and megakaryocytic cells expressed high levels of the IL-1b gene and produced IL-1b. Myeloma cells less potently expressed the IL-1b gene and IL-1b protein. IL-1b gene expression was not constitutive since it was detected in the bone marrow myeloma cells of two patients, unlike circulating tumoural cells. In addition, nine myeloma cell lines failed to express the IL-1b gene and this expression could not be induced by 12 different cytokines. We demonstrated that IL-1 was mainly responsible for IL-6 production in the tumoural environment through a PGE 2 loop. In fact, an IL-1 receptor antagonist (IL-1RA) blocked PGE 2 synthesis and IL-6 production by 80%; this blockage could be reversed by adding synthetic PGE 2 . Similar findings were found with indomethacin, an inhibitor of cyclooxygenase that blocks PGE 2 synthesis. Taken together, these data emphasize the possibility of blocking IL-1 by using IL-1RA or other antagonists in order to block IL-6 production, which is a major tumoural survival and proliferation factor.

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Section: Discussionsupporting

confidence: 93%

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confidence: 99%

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Interleukin‐1 in multiple myeloma: producer cells and their role in the control of IL‐6 production

et al. 1998

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“…This pleiotropic cytokine plays critical roles in a variety of inflammatory and non‐inflammatory diseases. Pathological functions have been demonstrated in rheumatoid arthritis 6–8, Alzheimer's disease 9, multiple myeloma 10 and leukaemia 11–13. Importantly for this study the involvement of IL‐1 in the inflamed intestinal mucosa is also well established.…”

Section: Introductionmentioning

confidence: 77%

IL‐1‐dependent, IL‐1R1‐independent resistance to gastrointestinal nematodes

Humphreys

Grencis

2009

Eur J Immunol

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IL-1 null mice are unable to expel the intestinal nematode Trichuris muris; whereas WT littermates exhibit sterile immunity. Intriguingly the essential signalling components IL-1R1 and IL-1R accessory protein (AcP) are dispensable for expulsion of this parasite. IL-1 is thus critical for CD41 Th2-mediated immunity to T. muris; however, this action is independent of the established IL-1 signalling receptor. We also present data demonstrating that both IL-1a and IL-1b induce measurable effects on T. muris primed cells isolated from IL-1R1 or IL-1R AcP null mice. MLN cells from these mice restimulated with parasite antigen proliferated at a greater rate and produced more cytokines in response to exogenous IL-1. This ability to respond to IL-1 was restricted to these parasite-primed cells and importantly was not evident in cells from naïve gene null mice. These in vitro data are consistent with the observed ability of mice with compromised IL-1 signalling to expel the parasite, bolstering the premise that an alternative IL-1 signalling mechanism is accessible in the context of an intestinal helminth-driven Th2 immune response.Key words: Cytokine . Infection . Parasitic-helminth . Proinflammatory . T cells IntroductionIL-1 is a potent molecule; indeed when unregulated the resultant inflammatory cytokine cascade has profound pathological effects [1,2]. Thus by necessity IL-1 bioactivity is tightly controlled, requiring both posttranslational processing and a signalling receptor containing IL-1R1 and IL-1R accessory protein (AcP). This pathway to IL-1 action is policed by a decoy receptor IL-1R2, a natural sink for IL-1 [3] and IL-1RA, which competitively binds IL-1R1, preventing IL-1RAcP recruitment and signal transduction [4]. Importantly, IL-1RA only weakly interacts with IL-1R2, thus preventing the inhibition of the inhibitor [5]. This pleiotropic cytokine plays critical roles in a variety of inflammatory and non-inflammatory diseases. Pathological functions have been demonstrated in rheumatoid arthritis [6][7][8], Alzheimer's disease [9], multiple myeloma [10] and leukaemia [11][12][13]. Importantly for this study the involvement of IL-1 in the inflamed intestinal mucosa is also well established. Patients with ulcerative colitis significantly over express , with the principle sources identified as colon subepithelial macrophages [19,20], follicular epithelial M cells [21] and lamina propria T cells [22]. IL-1 also influences adaptive immunity, altering the CD4 1 Th-cell balance, though published data demonstrate contradictory changes in both Th1 and Th2 immune polarisation [23][24][25][26][27][28]. For example, IL-1a/b null mice show reduced Th2 responses to ovalbumin-induced airway hypersensitivity [29,30], whereas conversely, IL-1a has been shown to enhance Th1-driven immunity to Leishmania major in BALB/c mice [31]. Thus understanding the interplay of IL-1 and T-cell polarisation is complex and highly dependent on model, strain of mouse and method of IL-1 manipulation. Here, to better understand this role of IL...

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“…2) including a variety of neoplastic processes. For example, it may affect cancer progression by its actions on cell adhesion and motility (36), thrombopoiesis (30,37), tumor specific antigen expression (38) and cancer cell (44,45), prostate carcinoma (46), Kaposi's sarcoma (47), ovarian carcinoma (48), lymphoma and leukemia (49)(50)(51), and multiple myeloma (52)(53)(54)(55)(56)(57)(58)(59). In many of these tumors, IL-6R have been detected and a direct proliferative signal has been proposed.…”

Section: Physiology and Pathophysiology Of Interleukin-6mentioning

confidence: 99%

Molecular and cellular biology of interleukin-6 and its receptor

1996

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Interleukin-6 (IL-6) is a member of the family of cytokines collectively termed "the interleukin-6 type cytokines." Among its many functions, IL-6 plays an active role in immunology, bone metabolism, reproduction, arthritis, neoplasia, and aging. IL-6 expression is regulated by a variety of factors, including steroidal hormones, at both the transcriptional and post-transcriptional levels. IL-6 achieves its effects through the ligand-specific IL-6 receptor (IL-6R). Unlike most other cytokine receptors, the IL-6R is active in both membrane bound and soluble forms. Defining mechanisms to control IL-6 or IL-6R expression may prove useful for therapy of the many clinical disorders in IL-6 plays a role.

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Interleukin-1 accelerates autocrine growth of myeloma cells through interleukin-6 in human myeloma

Cited by 10 publications

References 0 publications

Interleukin‐1 in multiple myeloma: producer cells and their role in the control of IL‐6 production

Interleukin‐1 in multiple myeloma: producer cells and their role in the control of IL‐6 production

IL‐1‐dependent, IL‐1R1‐independent resistance to gastrointestinal nematodes

Molecular and cellular biology of interleukin-6 and its receptor

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