Curcumin is a potent modulator of microglial gene expression and migration
<p>Abstract</p> <p>Background</p> <p>Microglial cells are important effectors of the neuronal innate immune system with a major role in chronic neurodegenerative diseases. Curcumin, a major component of tumeric, alleviates pro-inflammatory activities of these cells by i...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-09-01
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| Series: | Journal of Neuroinflammation |
| Online Access: | http://www.jneuroinflammation.com/content/8/1/125 |
| _version_ | 1818114486577397760 |
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| author | Aslanidis Alexander Moehle Christoph Walczak Yana Lippe Elena Karlstetter Marcus Mirza Myriam Langmann Thomas |
| author_facet | Aslanidis Alexander Moehle Christoph Walczak Yana Lippe Elena Karlstetter Marcus Mirza Myriam Langmann Thomas |
| author_sort | Aslanidis Alexander |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Microglial cells are important effectors of the neuronal innate immune system with a major role in chronic neurodegenerative diseases. Curcumin, a major component of tumeric, alleviates pro-inflammatory activities of these cells by inhibiting nuclear factor kappa B (NFkB) signaling. To study the immuno-modulatory effects of curcumin on a transcriptomic level, DNA-microarray analyses were performed with resting and LPS-challenged microglial cells after short-term treatment with curcumin.</p> <p>Methods</p> <p>Resting and LPS-activated BV-2 cells were stimulated with curcumin and genome-wide mRNA expression patterns were determined using DNA-microarrays. Selected qRT-PCR analyses were performed to confirm newly identified curcumin-regulated genes. The migration potential of microglial cells was determined with wound healing assays and transwell migration assays. Microglial neurotoxicity was estimated by morphological analyses and quantification of caspase 3/7 levels in 661W photoreceptors cultured in the presence of microglia-conditioned medium.</p> <p>Results</p> <p>Curcumin treatment markedly changed the microglial transcriptome with 49 differentially expressed transcripts in a combined analysis of resting and activated microglial cells. Curcumin effectively triggered anti-inflammatory signals as shown by induced expression of <it>Interleukin 4 </it>and <it>Peroxisome proliferator activated receptor α</it>. Several novel curcumin-induced genes including <it>Netrin G1</it>, <it>Delta-like 1</it>, <it>Platelet endothelial cell adhesion molecule 1</it>, and <it>Plasma cell endoplasmic reticulum protein 1</it>, have been previously associated with adhesion and cell migration. Consequently, curcumin treatment significantly inhibited basal and activation-induced migration of BV-2 microglia. Curcumin also potently blocked gene expression related to pro-inflammatory activation of resting cells including <it>Toll-like receptor 2 </it>and <it>Prostaglandin-endoperoxide synthase 2</it>. Moreover, transcription of <it>NO synthase 2 </it>and <it>Signal transducer and activator of transcription 1 </it>was reduced in LPS-triggered microglia. These transcriptional changes in curcumin-treated LPS-primed microglia also lead to decreased neurotoxicity with reduced apoptosis of 661W photoreceptor cultures.</p> <p>Conclusions</p> <p>Collectively, our results suggest that curcumin is a potent modulator of the microglial transcriptome. Curcumin attenuates microglial migration and triggers a phenotype with anti-inflammatory and neuroprotective properties. Thus, curcumin could be a nutraceutical compound to develop immuno-modulatory and neuroprotective therapies for the treatment of various neurodegenerative disorders.</p> |
| first_indexed | 2024-12-11T03:51:30Z |
| format | Article |
| id | doaj.art-f019b459563143ee86f0cdb242b558bb |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-11T03:51:30Z |
| publishDate | 2011-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-f019b459563143ee86f0cdb242b558bb2022-12-22T01:21:53ZengBMCJournal of Neuroinflammation1742-20942011-09-018112510.1186/1742-2094-8-125Curcumin is a potent modulator of microglial gene expression and migrationAslanidis AlexanderMoehle ChristophWalczak YanaLippe ElenaKarlstetter MarcusMirza MyriamLangmann Thomas<p>Abstract</p> <p>Background</p> <p>Microglial cells are important effectors of the neuronal innate immune system with a major role in chronic neurodegenerative diseases. Curcumin, a major component of tumeric, alleviates pro-inflammatory activities of these cells by inhibiting nuclear factor kappa B (NFkB) signaling. To study the immuno-modulatory effects of curcumin on a transcriptomic level, DNA-microarray analyses were performed with resting and LPS-challenged microglial cells after short-term treatment with curcumin.</p> <p>Methods</p> <p>Resting and LPS-activated BV-2 cells were stimulated with curcumin and genome-wide mRNA expression patterns were determined using DNA-microarrays. Selected qRT-PCR analyses were performed to confirm newly identified curcumin-regulated genes. The migration potential of microglial cells was determined with wound healing assays and transwell migration assays. Microglial neurotoxicity was estimated by morphological analyses and quantification of caspase 3/7 levels in 661W photoreceptors cultured in the presence of microglia-conditioned medium.</p> <p>Results</p> <p>Curcumin treatment markedly changed the microglial transcriptome with 49 differentially expressed transcripts in a combined analysis of resting and activated microglial cells. Curcumin effectively triggered anti-inflammatory signals as shown by induced expression of <it>Interleukin 4 </it>and <it>Peroxisome proliferator activated receptor α</it>. Several novel curcumin-induced genes including <it>Netrin G1</it>, <it>Delta-like 1</it>, <it>Platelet endothelial cell adhesion molecule 1</it>, and <it>Plasma cell endoplasmic reticulum protein 1</it>, have been previously associated with adhesion and cell migration. Consequently, curcumin treatment significantly inhibited basal and activation-induced migration of BV-2 microglia. Curcumin also potently blocked gene expression related to pro-inflammatory activation of resting cells including <it>Toll-like receptor 2 </it>and <it>Prostaglandin-endoperoxide synthase 2</it>. Moreover, transcription of <it>NO synthase 2 </it>and <it>Signal transducer and activator of transcription 1 </it>was reduced in LPS-triggered microglia. These transcriptional changes in curcumin-treated LPS-primed microglia also lead to decreased neurotoxicity with reduced apoptosis of 661W photoreceptor cultures.</p> <p>Conclusions</p> <p>Collectively, our results suggest that curcumin is a potent modulator of the microglial transcriptome. Curcumin attenuates microglial migration and triggers a phenotype with anti-inflammatory and neuroprotective properties. Thus, curcumin could be a nutraceutical compound to develop immuno-modulatory and neuroprotective therapies for the treatment of various neurodegenerative disorders.</p>http://www.jneuroinflammation.com/content/8/1/125 |
| spellingShingle | Aslanidis Alexander Moehle Christoph Walczak Yana Lippe Elena Karlstetter Marcus Mirza Myriam Langmann Thomas Curcumin is a potent modulator of microglial gene expression and migration Journal of Neuroinflammation |
| title | Curcumin is a potent modulator of microglial gene expression and migration |
| title_full | Curcumin is a potent modulator of microglial gene expression and migration |
| title_fullStr | Curcumin is a potent modulator of microglial gene expression and migration |
| title_full_unstemmed | Curcumin is a potent modulator of microglial gene expression and migration |
| title_short | Curcumin is a potent modulator of microglial gene expression and migration |
| title_sort | curcumin is a potent modulator of microglial gene expression and migration |
| url | http://www.jneuroinflammation.com/content/8/1/125 |
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