Modulation of inflammatory mediators via ibuprofen in tnf-α treated benign prostatic hyperplasia cells

Abstract

Benign prostatic hyperplasia (BPH) is one of the major diseases of the urinary system in elderly men. Many studies show that inflammation is closely linked to the development of BPH. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have effects of antipyretic and antinociceptive as well as anti-inflammatory but the data obtained regarding their use in the treatment of prostate related diseases such as BPH are contradictory. Therefore, the present study aimed to investigate the therapeutic potential of ibuprofen at low doses in the prevention and treatment of BPH. We perfottned MTT assay to investigate cell viability of BPH-1 cells, qRT-PCR to examine the mRNA levels of target cytokine genes and immunoblotting to assess the phosphorylation and total protein levels of NF kappa B signaling pathway. It was found that cell proliferation and viability with ibuprofen decreased only at high concentrations, approximately 500 mu M, as time dependent. Furthermore, it was determined that ibuprofen at low doses was effectively reduced TNF-alpha. induced IL1-alpha, IL-1-beta, IL-8 and IL-6 gene expression in a dose dependent manner. Additionally, in the presence of TNF-alpha, ibuprofen caused an increase in pNFKB-p65((ser536)) as 7.3 and 8.1 folds in a dose dependent manner, while led to a decrease in pI kappa B alpha((Ser32)) almost below basal level. The level of total NF kappa B-p65 protein level showed a steady increase in all applications. However, dramatic increases were observed for total I kappa B alpha protein level, especially in the combination of TNF-alpha and ibuprofen. For the first time, by this study, evidences have been obtained that in the presence of inflammatory agents, ibuprofen will support the resolution of inflammation by reducing cytokine release through modulating the I kappa B alpha phosphorylation and expression in NF kappa B signaling pathway. Consequently, NSAIDs such as ibuprofen should be further explored as a candidate for the prevention and treatment of BPH.