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,Benjamin Piura,Ruthy Shaco Levy,Victor Dyomin,Alex Rabinovich,Mahmoud Huleihel

doi:10.1155/2014/914954

Abstract

Proinflammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. The 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 significantly higher in cancerous ovarian tissues (P = 0.0007), IL-18BP levels were significantly higher in normal ovarian tissues (P = 0.04), and the ratio of IL-18/IL-18BP was significantly higher in cancerous ovarian tissues (P = 0.036). Cancerous ovarian tissues expressed significantly higher IL-18 mRNA levels (P = 0.025), while there was no difference 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. This study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma.

Highlights

Epithelial ovarian carcinoma (EOC) is the most frequent cause of death from gynecologic malignancies and the fifth leading cause of death from all cancers in women [1]
We have demonstrated that cancerous ovarian tissues (COT) express and secrete higher levels of IL-1α, IL-1β, IL-6, and TNF-α compared to normal ovarian tissues (NOT) and suggested that these cytokines may have a role in the pathogenesis of EOC [3,4,5,6,7,8]
The mean value of IL-18 levels expressed by positive COT samples was significantly higher compared to positive NOT samples: 0.2 ± 0.03 pg/μg protein and 0.07 ± 0.01 pg/μg protein, respectively (P = 0.0007) (Figure 1(a))

Summary

Introduction

Epithelial ovarian carcinoma (EOC) is the most frequent cause of death from gynecologic malignancies and the fifth leading cause of death from all cancers in women [1]. IL-18, formerly known as interferon-γ inducing factor [9], is a pleiotropic, proinflammatory cytokine with dual effects on tumor development and progression [10]. IL-18 induces T helper type 1 (Th1) immune response, which is generally regarded as the immune reaction that acts against malignant tumors. IL-18 promotes T helper type 2 (Th2) 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

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