Therapeutic targeting of Krüppel-like factor 4 abrogates microglial activation
<p>Abstract</p> <p>Background</p> <p>Neuroinflammation occurs as a result of microglial activation in response to invading micro-organisms or other inflammatory stimuli within the central nervous system. According to our earlier findings, Krüppel-like factor 4 (Klf4), a...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-03-01
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| Series: | Journal of Neuroinflammation |
| Online Access: | http://www.jneuroinflammation.com/content/9/1/57 |
| _version_ | 1811297677986496512 |
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| author | Kaushik Deepak Mukhopadhyay Rupanjan Kumawat Kanhaiya Gupta Malvika Basu Anirban |
| author_facet | Kaushik Deepak Mukhopadhyay Rupanjan Kumawat Kanhaiya Gupta Malvika Basu Anirban |
| author_sort | Kaushik Deepak |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Neuroinflammation occurs as a result of microglial activation in response to invading micro-organisms or other inflammatory stimuli within the central nervous system. According to our earlier findings, Krüppel-like factor 4 (Klf4), a zinc finger transcription factor, is involved in microglial activation and subsequent release of proinflammatory cytokines, tumor necrosis factor alpha, macrophage chemoattractant protein-1 and interleukin-6 as well as proinflammatory enzymes, inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated microglial cells. Our current study focuses on finding the molecular mechanism of the anti-inflammatory activities of honokiol in lipopolysaccharide-treated microglia with emphasis on the regulation of Klf4.</p> <p>Methods</p> <p>For <it>in vitro </it>studies, mouse microglial BV-2 cell lines as well as primary microglia were treated with 500 ng/mL lipopolysaccharide as well as 1 μM and 10 μM of honokiol. We cloned full-length Klf4 cDNA in pcDNA3.1 expression vector and transfected BV-2 cells with this construct using lipofectamine for overexpression studies. For <it>in vivo </it>studies, brain tissues were isolated from BALB/c mice treated with 5 mg/kg body weight of lipopolysaccharide either with or without 2.5 or 5 mg/kg body weight of honokiol. Expression of Klf4, cyclooxygenase-2, inducible nitric oxide synthase and phospho-nuclear factor-kappa B was measured using immunoblotting. We also measured the levels of cytokines, reactive oxygen species and nitric oxide in different conditions.</p> <p>Results</p> <p>Our findings suggest that honokiol can substantially downregulate the production of proinflammatory cytokines and inflammatory enzymes in lipopolysaccharide-stimulated microglia. In addition, honokiol downregulates lipopolysaccharide-induced upregulation of both Klf4 and phospho-nuclear factor-kappa B in these cells. We also found that overexpression of Klf4 in BV-2 cells suppresses the anti-inflammatory action of honokiol.</p> <p>Conclusions</p> <p>Honokiol potentially reduces inflammation in activated microglia in a Klf4-dependent manner.</p> |
| first_indexed | 2024-04-13T06:08:35Z |
| format | Article |
| id | doaj.art-17ac27dd5de3467cb1254de44dfe66fb |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-13T06:08:35Z |
| publishDate | 2012-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-17ac27dd5de3467cb1254de44dfe66fb2022-12-22T02:59:09ZengBMCJournal of Neuroinflammation1742-20942012-03-01915710.1186/1742-2094-9-57Therapeutic targeting of Krüppel-like factor 4 abrogates microglial activationKaushik DeepakMukhopadhyay RupanjanKumawat KanhaiyaGupta MalvikaBasu Anirban<p>Abstract</p> <p>Background</p> <p>Neuroinflammation occurs as a result of microglial activation in response to invading micro-organisms or other inflammatory stimuli within the central nervous system. According to our earlier findings, Krüppel-like factor 4 (Klf4), a zinc finger transcription factor, is involved in microglial activation and subsequent release of proinflammatory cytokines, tumor necrosis factor alpha, macrophage chemoattractant protein-1 and interleukin-6 as well as proinflammatory enzymes, inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated microglial cells. Our current study focuses on finding the molecular mechanism of the anti-inflammatory activities of honokiol in lipopolysaccharide-treated microglia with emphasis on the regulation of Klf4.</p> <p>Methods</p> <p>For <it>in vitro </it>studies, mouse microglial BV-2 cell lines as well as primary microglia were treated with 500 ng/mL lipopolysaccharide as well as 1 μM and 10 μM of honokiol. We cloned full-length Klf4 cDNA in pcDNA3.1 expression vector and transfected BV-2 cells with this construct using lipofectamine for overexpression studies. For <it>in vivo </it>studies, brain tissues were isolated from BALB/c mice treated with 5 mg/kg body weight of lipopolysaccharide either with or without 2.5 or 5 mg/kg body weight of honokiol. Expression of Klf4, cyclooxygenase-2, inducible nitric oxide synthase and phospho-nuclear factor-kappa B was measured using immunoblotting. We also measured the levels of cytokines, reactive oxygen species and nitric oxide in different conditions.</p> <p>Results</p> <p>Our findings suggest that honokiol can substantially downregulate the production of proinflammatory cytokines and inflammatory enzymes in lipopolysaccharide-stimulated microglia. In addition, honokiol downregulates lipopolysaccharide-induced upregulation of both Klf4 and phospho-nuclear factor-kappa B in these cells. We also found that overexpression of Klf4 in BV-2 cells suppresses the anti-inflammatory action of honokiol.</p> <p>Conclusions</p> <p>Honokiol potentially reduces inflammation in activated microglia in a Klf4-dependent manner.</p>http://www.jneuroinflammation.com/content/9/1/57 |
| spellingShingle | Kaushik Deepak Mukhopadhyay Rupanjan Kumawat Kanhaiya Gupta Malvika Basu Anirban Therapeutic targeting of Krüppel-like factor 4 abrogates microglial activation Journal of Neuroinflammation |
| title | Therapeutic targeting of Krüppel-like factor 4 abrogates microglial activation |
| title_full | Therapeutic targeting of Krüppel-like factor 4 abrogates microglial activation |
| title_fullStr | Therapeutic targeting of Krüppel-like factor 4 abrogates microglial activation |
| title_full_unstemmed | Therapeutic targeting of Krüppel-like factor 4 abrogates microglial activation |
| title_short | Therapeutic targeting of Krüppel-like factor 4 abrogates microglial activation |
| title_sort | therapeutic targeting of kruppel like factor 4 abrogates microglial activation |
| url | http://www.jneuroinflammation.com/content/9/1/57 |
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