Effects of a novel microtubule-depolymerizer on pro-inflammatory signaling in RAW264.7 macrophages
| Autor: | Anna L.K. Gonye, Krista Fischer-Stenger, Omar A. Quintero, Santiago Espinosa de los Reyes, Elizabeth C. Li, Samuel P. Gilmore, John T. Gupton |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Cell Survival Down-Regulation Inflammation Enzyme-Linked Immunosorbent Assay Toxicology Real-Time Polymerase Chain Reaction Article 03 medical and health sciences chemistry.chemical_compound Mice NF-KappaB Inhibitor alpha Microtubule medicine Macrophage Animals Pyrroles Phosphorylation Transcription factor Chemistry Macrophages NF-kappa B NF-κB General Medicine Tubulin Modulators Cell biology 030104 developmental biology medicine.anatomical_structure RAW 264.7 Cells Microscopy Fluorescence Cytokines medicine.symptom Signal transduction Inflammation Mediators Nucleus Signal Transduction |
| Zdroj: | Chemico-biological interactions. 280 |
| ISSN: | 1872-7786 |
| Popis: | The Nuclear Factor-kappa B (NF-κB) pathway is vital for immune system regulation and pro-inflammatory signaling. Many inflammatory disorders and diseases, including cancer, are linked to dysregulation of NF-κB signaling. When macrophages recognize the presence of a pathogen, the signaling pathway is activated, resulting in the nuclear translocation of the transcription factor, NF-κB, to turn on pro-inflammatory genes. Here, we demonstrate the effects of a novel microtubule depolymerizer, NT-07-16, a polysubstituted pyrrole compound, on this process. Treatment with NT-07-16 decreased the production of pro-inflammatory cytokines in RAW264.7 mouse macrophages. It appears that the reduction in pro-inflammatory mediators produced by the macrophages after exposure to NT-07-16 may be due to activities upstream of the translocation of NF-κB into the nucleus. NF-κB translocation occurs after its inhibitory protein, IκB-α is phosphorylated which signals for its degradation releasing NF-κB so it is free to move into the nucleus. Previous studies from other laboratories indicate that these processes are associated with the microtubule network. Our results show that exposure to the microtubule-depolymerizer, NT-07-16 reduces the phosphorylation of IκB-α and also decreases the association of NF-κB with tubulin which may affect the ability of NF-κB to translocate into the nucleus. Therefore, the anti-inflammatory activity of NT-07-16 may be explained, at least in part, by alterations in these steps in the NF-κB signaling pathway leading to less NF-κB entering the nucleus and reducing the production of pro-inflammatory mediators by the activated macrophages. |
| Databáze: | OpenAIRE |
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