| Title | Evidence for a pathophysiological role of cysteinyl leukotrienes in classical Hodgkin lymphoma. | | Author(s) | Schain F, Tryselius Y, Sjöberg J, Porwit A, Backman L, Malec M, Xu D, Vockerodt M, Baumforth KR, Wei W, Murray PG, Björkholm M, Claesson HE | | Institution | Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden. frida.schain@ki.se | | Source | Int J Cancer 2008 Nov 15; 123(10):2285-93. | | MeSH | Adolescent
Adult
Aged
Calcium Signaling
Cell Line, Tumor
Child
Child, Preschool
Cysteine
Female
Hodgkin Disease
Humans
Immunohistochemistry
Leukotriene D4
Leukotrienes
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
Receptors, Leukotriene
| | Abstract | Classical Hodgkin lymphoma (cHL) is characterized histologically by a minority of malignant Hodgkin Reed-Sternberg cells surrounded by abundant inflammatory cells, generally believed to be of major importance in the pathophysiology of the disease. Here, we present data that link inflammatory cell-derived arachidonic acid metabolites, the cysteinyl leukotrienes (CysLT), to the pathogenesis of cHL. Two HL cell lines, L1236 and KMH2, were shown to express functional CysLT(1) receptors, responding with a robust calcium signal upon leukotriene (LT) D(4) challenge. LTD(4) stimulated protein release of tumor necrosis factor-alpha, interleukin-6 and -8 by L1236 cells and interleukin-8 by KMH2 cells. Importantly, all these LTD(4)-induced effects were blocked by the CysLT(1) receptor-specific antagonist zafirlukast. Immunohistochemical studies of cHL biopsies and microarray analysis of microdissected cells revealed that the CysLT(1) receptor is expressed also by primary Hodgkin Reed-Sternberg cells. As these cells are surrounded by CysLT-producing eosinophils, macrophages and mast cells, our results suggest the CysLTs as mediators in the pathogenesis of cHL, contributing to the aberrant cytokine network of this lymphoma. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 18704935 |
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