The role of macrophage migration inhibitory factor in promoting benign prostatic hyperplasia epithelial cell growth by modulating COX-2 and P53 signaling

• Main Authors: Hualin Song, Qi Shen, Shuai Hu, Jie Jin
• Format: Article
• Language: English
• Published: The Company of Biologists 2020-11-01
• Series: Biology Open
• Subjects: benign prostatic hyperplasia; proliferation; mif; cox-2; p53
• Online Access: http://bio.biologists.org/content/9/11/bio053447

Inflammation and proinflammatory cytokines have been implicated in the progression of benign prostatic hyperplasia (BPH). Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine. Our previous study found that MIF is highly expressed in BPH epithelium. It has been reported that there is a correlation between MIF and clinical BPH progression. However, whether MIF has an effect on BPH epithelial cells is not clear. The aim of this study was to explore whether MIF has a role in BPH. Our results showed that immunohistochemistry (IHC) showed that MIF is highly expressed in the epithelium and that MIF and PCNA expression levels are higher in BPH samples than in control. CCK8 and flow cytometry assays showed that recombinant human MIF (rMIF) promoted the proliferation of BPH-1 and PWR-1E cells, while ISO-1 partially reversed this effect on proliferation. JC-1 assays showed that rMIF inhibited the apoptosis of BPH-1 and PWR-1E cells, and ISO-1 could partially reverse this inhibition. Moreover, western blotting indicated that rMIF downregulated P53 and upregulated COX-2. Furthermore, MIF-induced proliferation could be inhibited by celecoxib in the CCK8 and flow cytometry assay. MIF-inhibited apoptosis could be partially reversed by celecoxib in the JC-1 assay. Western blotting showed that celecoxib could partially reverse MIF-induced COX-2 upregulation and P53 downregulation. Together, MIF is highly expressed in BPH epithelium. In vitro, MIF promoted BPH epithelial cell growth by regulating COX-2 and P53 signaling. Targeting MIF may provide a new option for the improved treatment of BPH in the future.