title: Interleukin-1β orchestrates underlying inflammatory responses in microglia via Krüppel-like factor 4.
abstract: 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.
authors.affiliation: National Brain Research Centre, Manesar, Haryana, India.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Kaushik
authors.forename: Menaka C
authors.initials: MC
authors.lastname: Thounaojam
authors.forename: Kanhaiya L
authors.initials: KL
authors.lastname: Kumawat
authors.forename: Malvika
authors.initials: M
authors.lastname: Gupta
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D053583:Interleukin-1beta / Q000494:pharmacology* / Q000502:physiology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000071245:Mitochondrial Uncoupling Proteins; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D053583:Interleukin-1beta; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins; C492124:Slc25a14 protein, mouse; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D051058:Oncogene Protein v-akt
keywords: Krüppel-like factor 4; brain; cytokines; iNOS; neuroinflammation