Interleukin-1β orchestrates underlying inflammatory responses in microglia via Krüppel-like factor 4
| Autor: | Malvika Gupta, Anirban Basu, Menaka C. Thounaojam, Deepak Kumar Kaushik, Kanhaiya Lal Kumawat |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Chromatin Immunoprecipitation MAP Kinase Signaling System Blotting Western Interleukin-1beta Kruppel-Like Transcription Factors Nitric Oxide Synthase Type II Nerve Tissue Proteins Biology Real-Time Polymerase Chain Reaction Transfection Biochemistry Cell Line Proinflammatory cytokine Kruppel-Like Factor 4 Mice Cellular and Molecular Neuroscience medicine Animals Phosphorylation Neuroinflammation PI3K/AKT/mTOR pathway Inflammation Mice Knockout Mice Inbred BALB C Microglia Monocyte Chemotaxis Immunohistochemistry Cell biology Oncogene Protein v-akt Nitric oxide synthase medicine.anatomical_structure nervous system Cyclooxygenase 2 KLF4 Mutagenesis Site-Directed biology.protein Cytokines Female Mitochondrial Uncoupling Proteins Carrier Proteins Neuroscience |
| Zdroj: | Journal of Neurochemistry. 127:233-244 |
| ISSN: | 0022-3042 |
| DOI: | 10.1111/jnc.12382 |
| Popis: | Microglia are the resident macrophages of the CNS, which secrete several pro- and anti-inflammatory cyto-chemokines including interleukin-1β (IL-1β), in response to pathogenic stimuli. Once secreted, IL-1β binds to IL-1 receptor present on microglia and initiates the production of inflammatory cytokines in microglia. However, the detailed information regarding the molecular mechanisms of IL-1β triggered inflammatory pathways in microglia is lacking. Our studies focused on the role of Krüppel-like factor 4 (Klf4) in mediating the regulation of pro-inflammatory gene expression upon IL-1β stimulation in microglia. Our studies show that stimulation of microglia with IL-1β robustly induces Klf4 via PI3K/Akt pathway which positively regulates the production of endogenous IL-1β as well as other pro-inflammatory markers, cyclooxygenase-2, monocyte chemoattractant protein-1 and interleukin-6 (IL-6). In addition, we report that Klf4 negatively regulates the expression of inducible nitric oxide synthase, thereby playing a key role in regulating the immunomodulatory activities of microglia. |
| Databáze: | OpenAIRE |
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