Effects of a pyrrole-based, microtubule-depolymerizing compound on RAW 264.7 macrophages

RAW 264.7 murine macrophages were exposed to the pyrrole-based compound 3,5-Dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester (JG-03-14), which is a known microtubule depolymerizing agent with antitumor activity [1,2,3]. In this study exposure to JG-03-14 reduced the production of pro-inflammatory molecules by macrophages activated with lipopolysaccharide (LPS). Treatment with the pyrrole-based compound decreased the concentration of tumor necrosis factor-a (TNF-alpha) and nitric oxide (NO) released from the macrophages. Exposure to JG-03-14 also decreased TNF-alpha mRNA expression levels and the protein expression levels of inducible nitric oxide synthase (iNOS), the enzyme responsible for NO production in the activated macrophages. Furthermore, JG-03-14 treatment significantly changed the degradation profile of I kappa B-beta, an inhibitor of the NF-kappa B transcription factor, which suggests that JG-03-14 may attenuate the activation of the LPS-induced NF-kappa B signaling pathway needed to produce the pro-inflammatory mediators. We conclude that JG-03-14 possesses anti-inflammatory properties. (C) 2016 Elsevier Ireland Ltd. All rights reserved.