title: Effects of a pyrrole-based, microtubule-depolymerizing compound on RAW 264.7 macrophages.
abstract: 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-α (TNF-α) and nitric oxide (NO) released from the macrophages. Exposure to JG-03-14 also decreased TNF-α 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 IκB-β, an inhibitor of the NF-κB transcription factor, which suggests that JG-03-14 may attenuate the activation of the LPS-induced NF-κB signaling pathway needed to produce the pro-inflammatory mediators. We conclude that JG-03-14 possesses anti-inflammatory properties.
authors.affiliation: Department of Biology, University of Richmond, Richmond, VA 23173, United States. Electronic address: john.ciemniecki@richmond.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Ciemniecki
authors.affiliation: Department of Biology, University of Richmond, Richmond, VA 23173, United States. Electronic address: clarke.lewis@richmond.edu.
authors.forename: Clarke P
authors.initials: CP
authors.lastname: Lewis
authors.affiliation: Department of Chemistry, University of Richmond, Richmond, VA 23173, United States. Electronic address: jgupton@richmond.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Gupton
authors.affiliation: Department of Biology, University of Richmond, Richmond, VA 23173, United States. Electronic address: kstenger@richmond.edu.
authors.forename: Krista
authors.initials: K
authors.lastname: Fischer-Stenger
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D058105:Polymerization / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C521391:3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051550:I-kappa B Kinase
keywords: Inflammation; JG-03-14 pyrrole compound; NF-κB; Nitric oxide; RAW264.7 macrophages; TNF-α