The Profile of Prostate Epithelial Cytokines and its Impact on Sera Prostate Specific Antigen Levels
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The Profile of Prostate Epithelial Cytokines and its Impact on Sera Prostate Specific Antigen Levels Yosra Bouraoui Mechergui,1 Awatef Ben Jemaa,1 Chekib Mezigh,2 Benito Fraile,3 Nawfel Ben Rais,4 Ricardo Paniagua,3 Mar Royuela,3 and Ridha Oueslati1,5
Abstract—The aim of this study was determined the expression of pro inflammatory cytokines in prostate epithelial cells. Furthermore, we analysed the relation between these cytokines and sera PSA levels according the three groups: 0–4, 4–20 and >20 ng/mL. The study was carried out in five normal prostate (NP), 27 benign prostate hyperplastic (BPH) and 18 prostate cancer (PC). Immunohistochemical and Western blot analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser. The western Blotting analysis revealed an immunoexpression of IL-1α, IL-6 and TNFα in BPH and PC. IL1α, was absent in NP. Immunohistochemical analysis showed significant high optical density to IL-1α and IL-6 in cancer epithelial cells (19.45±3.25 and 26.2±3.19) compared to normal cells (1.73±1.51 and 4.83 ±2.65). While, TNFα optical densities were not significant in NP (12.03±2.9), BPH (9.87±3.85) and PC (13.34±2.34). The different profiles of cytokines according sera PSA levels showed a high immunoexpression of the profile (IL-6+, IL-1α+) in BPH patients with PSA between 0–4 and 4–20 ng/mL. However, PC patients with sera PSA between 4 and 20 ng/mL, showed a significant high immunoexpression of the profile (IL-6+, IL-1α−). This data demonstrate a locally production of pro-inflammatory cytokines by prostate epithelial cells and a cross talk between PSA and these cytokines in prostate pathologies. KEY WORDS: prostate specific antigen (PSA); benign hyperplasia prostate; prostate cancer; epithelial cells; pro inflammatory cytokines; IL-1α; IL-6; TNFα.
cytokines [2]. Chronic or recurrent inflammation is responsible for the development of many human cancers including prostate cancer [3]. Epithelial cells have the capacity to secrete a wide range of cytokines which can regulate cell growth and immune or inflammatory responses. Intestinal, lungs and limbal epithelial cells have been shown produce pro-inflammatory cytokines such as IL-1, IL-6 and TNFα [4–6]. The prostate epithelial cells have been also shown to produce proinflammatory cytokine in androgen-dependant and androgen-independent prostate cells and influence the growth and differentiation of normal and prostate cancer cells [7, 8]. Androgens regulate the expression of androgen-regulated genes such as prostate specific antigen (PSA) through the binding of the androgen receptor (AR) to the androgen-responsive elements (AREs) in the promoter of PSA [9, 10]. Signalling pathways activated by cytokines such IL-6 and IL-4
INTRODUCTION Cytokines are released in response to a diverse of cellular stresses including carcinogen-induced injury, infection and inflammation [1]. Some cytokines clearly promote inflammation and act to make disease worse and are called pro inflammatory cytokines, whereas other cytokines serve to reduce inflammation and promote healin
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