Sex hormone modulation of cell growth and apoptosis of the human monocytic/macrophage cell line

Experimental and clinical evidence indicates that immune reactivity is greater in females than in males and suggests that gonadal steroids may play an important role in the regulation of the immune response [1-4]. Indeed, many cells of the immune system have been found to possess functional sex hormone receptors, such as CD8-positive T cells, B cells and, notably, monocytes/macrophages [5,6].Therefore, 17β-oestradiol (E2) was found to inhibit cellular apoptosis, to increase antibody production by B cells and to exert dose-related effects on T-cell functions [7]. Androgens seem to exert effects opposite to those of E2 on immune response [8]. Clinical epidemiology clearly confirms a higher prevalence of autoimmune diseases in female subjects when compared with male subjects [9].The studies concerning the functional interaction between the NF-κB pathway and members of the steroid hormone receptor family, and their role in synovial inflammation, have advanced significantly, although with controversial results [10,11]. In particular, after binding with E2, oestrogen receptors have been shown to interact with NF-κB factors, via transcriptional co-factors, resulting in mutual or non-mutual antagonism. Other studies hypothesize that, since oestrogen receptors may repress both constitutive and inducible NF-κB activity, the overexpression of NF-κB-inducible genes in oestrogen receptor-negative cells might contribute to malignant cell growth and chemotherapeutic resistance [12,13]. On the contrary, further studies report that E2 blocks the transcriptional activity of p65 in macrophages [14]. However, these opposite observations arise using different cell lines (human/animals) and culture conditions as well as different hormone concentrations [15]. In addition, multiple mechanisms concerning the interaction between oestrogen receptors and NF-κB have been proposed, such as repression of NF-κB DNA binding by physical association with oestrogen receptors and the regulation of IκB-