Expression of Interleukin-1 and Interleukin-1 Receptors Type 1 and Type 2 in Hodgkin Lymphoma

• Published in: PloS one 2015-09, Vol.10 (9), p.e0138747-e0138747
• Main Authors: Oelmann, Elisabeth, Stein, Harald, Berdel, Wolfgang E, Herbst, Hermann
• Format: Article
• Language: English
• Subjects: Cancer; Case-Control Studies; Cytokines; Disease control; Endothelial cells; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; Fibrosis; Gene Expression Regulation, Neoplastic; Hematology; Hodgkin Disease - blood; Hodgkin Disease - genetics; Hodgkin Disease - metabolism; Hodgkin's disease; Hodgkin's lymphoma; Humans; Immune response; Immune system; Interleukin 1; Interleukin 1 receptors; Interleukin-1 - genetics; Interleukin-1 - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Intracellular; Lymphocytes; Lymphoma; Male; Paracrine signalling; Patients; Plasma; Receptors; Receptors, Interleukin-1 Type I - blood; Receptors, Interleukin-1 Type I - genetics; Receptors, Interleukin-1 Type I - metabolism; Receptors, Interleukin-1 Type II - blood; Receptors, Interleukin-1 Type II - genetics; Receptors, Interleukin-1 Type II - metabolism; Remission; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal transduction; Transcription; Tumor cells; Viruses; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138747

Signaling through the IL-1-receptor type 1 (IL-1R1), IL-1 is required for initiation and maintenance of diverse activities of the immune system. A second receptor, IL-1R2, blocks IL-1 signal transduction. We studied expression of IL-1beta, IL-1R1, and IL-1R2 in 17 Hodgkin lymphomas (HL) by in situ hybridization (ISH). IL-1beta expressing cells, morphologically consistent with endothelial cells and fibroblasts, occurred in all HL tissues with elevated transcript levels in areas of active fibrosis. Hodgkin and Reed-Sternberg (HRS) cells of all cases expressed low IL-1R1 transcript levels in some tumor cells, and high levels of IL-1R2 in large proportions of HRS cells. Only few bystander cells showed low levels of IL-1R1 and IL-1R2 RNA. Supernatants of 4 out of 7 HL-derived cell lines contained soluble IL-1R2 protein at high levels. HL patient sera carried variably amounts of IL-1R2 protein with significantly increased titers in patients with active disease compared to patients in complete remission and control individuals without HL. Western blots and co-immunoprecipitations showed binding of the IL-1R2 to the intracellular IL-1R-accessory protein (IL-1IRAcP). These data suggest functions of the IL-1R2 as a "decoy-receptor" sequestrating paracrine IL-1 extracellularly and intracellularly by engaging IL-1IRAcP, thus depriving IL1-R1 molecules of their extracellular and intracellular ligands. Expression of IL1-R2 by HRS cells seems to contribute to local and systemic modulation of immune function in HL.