Curcumin is a potent modulator of microglial gene expression and migration

Background: 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.methods: 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.results: 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 interleukin 4 and peroxisome proliferator activated receptor α. several novel curcumin-induced genes including netrin g1,delta-like 1,platelet endothelial cell adhesion molecule 1,and plasma cell endoplasmic reticulum protein 1,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 toll-like receptor 2 and prostaglandin-endoperoxide synthase 2. moreover,transcription of no synthase 2 and signal transducer and activator of transcription 1 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.conclusions: 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. © 2011 karlstetter et al; licensee biomed central ltd.