DISTINCT PATTERNS OF EXPRESSION OF INTERLEUKIN-1-ALPHA AND INTERLEUKIN-1-BETA BY NORMAL AND CANCEROUS HUMAN OVARIAN TISSUES

Immunohistochemical staining of normal and cancerous ovarian tissues h as demonstrated that both IL-1 alpha and IL-1 beta are more strongly e xpressed in cancerous than in normal tissues and are secreted mainly b y epithelial cells, We have shown by bioassay and immunoassay that can cerous, but not normal ovarian tissues constitutively secrete IL-1 in vitro, Activation of cancerous ovarian tissues by lipopolysaccharide ( LPS) increased its capacity to secrete IL-1, Normal ovarian tissues se creted low amounts of IL-1 only after prolonged stimulation (72-96 h) by high doses of Ups (10-100 mu g/ml). On the other hand, constitutive IL-1 was detected in homogenates of normal ovarian tissues and stimul ation by LPS increased its capacity to produce IL-1. IL-1 beta was the main type of IL-1 secreted by cancerous ovarian tissues, IL-1 alpha w as detected at lower levels, In contrast, in normal tissues similar am ounts of both IL-1 alpha and IL-1 beta were detected in the supernatan ts, The levels of both types of IL-1, and also the bioactivity of IL-1 were significantly higher in cancerous than in normal ovarian tissues . Established primary cell lines from normal ovarian tissues did not s ecrete IL-1 into supernatants but did express it at very low levels, S timulation with EPS did not affect the capacity of these cell lines to secrete IL-1 but it increased their capacity to express it, In contra st, primary established epithelial cell lines from cancerous ovarian t issues did secrete and express high levels of IL-1 and these levels we re increased under stimulation with LPS, Cancerous ovarian tissues did not only secrete higher levels of both IL-1 alpha and beta than norma l ovarian tissues, but also the mechanism controlling the secretion of these factors in cancerous ovarian tissues seemed to be different fro m that found in normal ovarian tissues, Our results suggest that parac rine/autocrine factors may be involved in the regulation of both types of IL-1 secreted by ovarian tissues, These cytokines may play a role in regulating the physiological, pathophysiological and oncogenic proc esses of the ovary.