Research Article Expression of IL-18, IL-18 Binding Protein, and IL-18 Receptor by Normal and Cancerous Human Ovarian Tissues: Possible Implication of IL-18 in the Pathogenesis of Ovarian Carcinoma Liat Medina, 1,2 Alex Rabinovich, 2,3 Benjamin Piura, 2,3 Victor Dyomin, 3,4 Ruthy Shaco Levy, 3,4 and Mahmoud Huleihel 1,2 1 Te Shraga Segal Department of Microbiology, Immunology and Genetics, Be’er Sheva, Israel 2 Faculty of Health Sciences, Ben-Gurion University of the Negev, 84105 Be’er Sheva, Israel 3 Unit of Gynecologic Oncology, Division of Obstetrics and Gynecology, Soroka University Medical Center, 84105 Be’er Sheva, Israel 4 Institute of Pathology, Soroka University Medical Center, 84105 Be’er Sheva, Israel Correspondence should be addressed to Mahmoud Huleihel; huleihel@bgu.ac.il Received 27 January 2014; Accepted 15 April 2014; Published 15 May 2014 Academic Editor: Magdalena Klink Copyright © 2014 Liat Medina et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Proinfammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. Te aim of the study was to examine the levels and cellular origin of IL-18, IL-18 binding protein, and IL-18 receptor in normal and cancerous ovarian tissues. Ovarian tissue samples were examined by immunohistochemical staining for IL-18, IL-18BP, and IL-18R and mRNA of these cytokines was analyzed with semiquantitative PT-PCR. IL-18 levels were signifcantly higher in cancerous ovarian tissues ( = 0.0007), IL-18BP levels were signifcantly higher in normal ovarian tissues ( = 0.04), and the ratio of IL-18/IL-18BP was signifcantly higher in cancerous ovarian tissues ( = 0.036). Cancerous ovarian tissues expressed signifcantly higher IL-18 mRNA levels ( = 0.025), while there was no diference in the expression of IL-18BP mRNA and IL-18R mRNA between cancerous and normal ovarian tissues. IL-18 and IL-18BP were expressed dominantly in the epithelial cells of both cancerous and normal ovarian tissues, while IL-18R was expressed dominantly in the epithelial cells of cancerous ovarian tissues but expressed similarly in the epithelial and stromal cells of normal cancerous tissues. Tis study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma. 1. Introduction Epithelial ovarian carcinoma (EOC) is the most frequent cause of death from gynecologic malignancies and the ffh leading cause of death from all cancers in women [1]. Te cytokine network in the tumor microenvironment may be involved in many aspects of tumor growth and spread such as proliferation, motility, survival, cell-cell or cell-matrix adhesion, neovascularization, extracellular matrix remodel- ing, host cell infltration, and local immune response [2]. In previous studies, we have demonstrated that cancerous ovarian tissues (COT) express and secrete higher levels of IL-1, IL-1, IL-6, and TNF- compared to normal ovarian tissues (NOT) and suggested that these cytokines may have a role in the pathogenesis of EOC [3–8]. IL-18, formerly known as interferon- inducing factor [9], is a pleiotropic, proinfammatory cytokine with dual efects on tumor development and progression [10]. On the one hand, IL-18 induces T helper type 1 (T1) immune response, which is generally regarded as the immune reaction that acts against malignant tumors. On the other hand, IL-18 promotes T helper type 2 (T2) immune responses that may inhibit recognition of cancer cells by immune cells, increase the adhesion molecules, induce production of angiogenic factors, and promote a prometastatic microenvironment [11, 12]. IL-18 belongs to the IL-1 family of ligands [13]; it has 12% homology Hindawi Publishing Corporation Mediators of Inflammation Volume 2014, Article ID 914954, 8 pages http://dx.doi.org/10.1155/2014/914954