Hodgkin Reed–Sternberg cells express 15‐lipoxygenase‐1 and are putative producers of eoxins in vivo

Abstract

Classical Hodgkin lymphoma has unique clinical and pathological features and tumour tissue is characterized by a minority of malignant Hodgkin Reed–Sternberg cells surrounded by inflammatory cells. In the present study, we report that the Hodgkin lymphoma‐derived cell line L1236 has high expression of 15‐lipoxygenase‐1 and that these cells readily convert arachidonic acid to eoxin C4, eoxin D4 and eoxin E4. These mediators were only recently discovered in human eosinophils and mast cells and found to be potent proinflammatory mediators. Western blot and immunocytochemistry analyses of L1236 cells demonstrated that 15‐lipoxygenase‐1 was present mainly in the cytosol and that the enzyme translocated to the membrane upon calcium challenge. By immunohistochemistry of Hodgkin lymphoma tumour tissue, 15‐lipoxygenase‐1 was found to be expressed in primary Hodgkin Reed–Sternberg cells in 17 of 20 (85%) investigated biopsies. The enzyme 15‐lipoxygenase‐1, however, was not expressed in any of 10 biopsies representing nine different subtypes of non‐Hodgkin lymphoma. In essence, the expression of 15‐lipoxygenase‐1 and the putative formation of eoxins by Hodgkin Reed–Sternberg cells in vivo are likely to contribute to the inflammatory features of Hodgkin lymphoma. These findings may have important diagnostic and therapeutic implications in Hodgkin lymphoma. Furthermore, the discovery of the high 15‐lipoxygenase‐1 activity in L1236 cells demonstrates that this cell line comprises a useful model system to study the chemical and biological roles of 15‐lipoxygenase‐1.

Reactive oxygen species and lipoxygenases regulate the oncogenicity of NPM-ALK-positive anaplastic large cell lymphomas

“…A second paper demonstrated that 15-LOX was strongly expressed in Hodgkin Reed-Sternberg cells and pointed to the importance of LOX as potential therapeutic targets in malignant hemopathies. In this same study, the authors confirmed the absence of 15-LOX mRNA in several non-Hodgkin's lymphomas, but the role of ROS or LOX enzymes in ALCLs has so far never been investigated (Claesson et al, 2008).…”

The Kaposi's Sarcoma-Associated Herpesvirus (KSHV)-Induced 5-Lipoxygenase-Leukotriene B4 Cascade Plays Key Roles in KSHV Latency, Monocyte Recruitment, and Lipogenesis

“…LTB4 has been shown to impact the immune response and spread of viral infections, including those caused by HIV, respiratory syncytial virus, and Epstein-Barr virus (EBV) (44)(45)(46)(47)(48)(49). 5LO, LTA4H, and LTB4 are found at high levels in most of the inflammation and oxidative stress-associated cancers, such as breast, lung, prostate, pancreatic, colon, bladder, esophageal, and testicular cancers; glioma; chronic myelogenous leukemia; and Mantle cell lymphoma (MCL) non-Hodgkin's lymphomas (41,42,(50)(51)(52)(53)(54). 5LO pathway inhibitors have been tested as chemoprevention agents in many cancers (55,56).…”

Development of a Fluorescent Intensity Assay Amenable for High-Throughput Screening for Determining 15-Lipoxygenase Activity

“…7 We have used this cell assay to develop a microplate assay that is amenable for screening and for determination of inhibitory potency. To establish basic assay conditions, we titrated the amount of substrate and also investigated the linearity of product formation with respect to incubation time (Suppl.…”

“…9,10 Ovalbumin-sensitized 12/15-LO null mice display reduced airway inflammation, reduced cytokine production, and less proliferation of airway epithelial cells after exposure of allergen. 11,12 There are also reports suggesting that 15-LO-1 is involved in pathological processes such as cytokine release from airway epithelial cells, 13 cardiac inflammation, 14 atherosclerosis, [15][16][17] Alzheimer's disease, 18 Hodgkin's lymphoma, 7 and latent insulin resistance and diabetic nephropathy. 19,20 Also, 15-LO-1 inhibitors have been shown to rescue neuronal cells from cell death induced by oxidative stress.…”

“…This hydroperoxide can function as a substrate for glutathione transferases, leading to the formation of eoxin C 4 (EXC 4 ). 7,8 The enzyme 15-LO-1, or its rodent ortholog 12/15-LO, has been implicated in pro-as well as anti-inflammatory processes. 9,10 Ovalbumin-sensitized 12/15-LO null mice display reduced airway inflammation, reduced cytokine production, and less proliferation of airway epithelial cells after exposure of allergen.…”