Effects of Polysubstituted Pyrroles on Pro-Inflammatory Signaling in RAW264.7 Macrophages
Annie Wang, Anna Mann
An acute inflammatory response occurs when macrophages detect the presence of a pathogen in tissues, which leads to the activation of several signaling pathways resulting in the production of pro-inflammatory molecules by these cells. Previous studies from our laboratory have demonstrated that polysubstituted pyrroles that are known microtubule-depolymerizers possess anti-inflammatory activity in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Since microtubules play a critical role in cell physiology, compounds that target the microtubule network have been studied for their potential use as chemotherapeutic agents. We have shown that exposure to these pyrroles decreases the production of pro-inflammatory cytokines in RAW264.7 cells by attenuating the NF-?B signaling pathway. This anti-inflammatory activity may be explained, at least in part, by reducing the nuclear translocation of NF-?B, which results in a decrease in the production of pro-inflammatory mediators by activated macrophages. Here, we have examined the effects of these compounds on additional pro-inflammatory pathways.