Curcumin (diferulolylmethane) demonstrates profound anti-inflammatory effects in intestinal epithelial cells (IEC) and in immune cells in vitro and exhibits a protective role in rodent models of chemically induced colitis, with its presumed primary mechanism of action via inhibition of NF-κB. Although it has been demonstrated effective in reducing relapse rate in ulcerative colitis patients, curcumin's effectiveness in Crohn's disease (CD) or in Th-1/Th-17 mediated immune models of CD has not been evaluated. Therefore, we investigated the effects of dietary curcumin (0.1–1%) on the development of colitis, immune activation, and in vivo NF-κB activity in germ-free IL-10 –/– or IL-10 –/– ;NF-κB EGFP mice colonized with specific pathogen-free microflora. Proximal and distal colon morphology showed a mild protective effect of curcumin only at 0.1%. Colonic IFN-γ and IL-12/23p40 mRNA expression followed similar pattern (∼50% inhibition at 0.1%). Secretion of IL-12/23p40 and IFN-γ by colonic explants and mesenteric lymph node cells was elevated in IL-10 –/– mice and was not decreased by dietary curcumin. Surprisingly, activation of NF-κB in IL-10 –/– mice (phospho-NF-κBp65) or in IL-10 –/– ;NF-κB EGFP mice (whole organ or confocal imaging) was not noticeably inhibited by curcumin. Furthermore, we demonstrate that IL-10 and curcumin act synergistically to downregulate NF-κB activity in IEC and IL-12/23p40 production by splenocytes and dendritic cells. In conclusion, curcumin demonstrates limited effectiveness on Th-1 mediated colitis in IL-10 –/– mice, with moderately improved colonic morphology, but with no significant effect on pathogenic T cell responses and in situ NF-κB activity. In vitro studies suggest that the protective effects of curcumin are IL-10 dependent. inflammatory bowel disease; Crohn's disease; NF-κB Address for reprint requests and other correspondence: P. R. Kiela, Dept. of Pediatrics, Steele Children's Research Center, Univ. of Arizona Health Sciences Center; 1501 N. Campbell Ave., Tucson, AZ 85724 (e-mail: pkiela@peds.arizona.edu )
End of preview. The entire article is 14 pages. To view the full-text, please rent this article to continue.
/lp/the-american-physiological-society/limited-effects-of-dietary-curcumin-on-th-1-driven-colitis-in-il-10-dQYMvEmwYL
Welcome to DeepDyve! Rent Premier Research Articles and Save Up to 90%
Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice suggest an IL-10-dependent mechanism of protection
Larmonier, C. B.; Uno, J. K.; Lee, Kang-Moon; Karrasch, T.; Laubitz, D.; Thurston, R.; Midura-Kiela, M. T.; Ghishan, F. K.; Sartor, R. B.; Jobin, C.; Kiela, P. R.
Follow AJP - Gastrointestinal and Liver Physiology
, Volume 295 (5): G1079
The American Physiological Society – Nov 1, 2008
More Info
More Like This Article
View All dataSource[]=actageo&dataSource[]=aspet&dataSource[]=aaos&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aea&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=ams&dataSource[]=aps_physical&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=apha&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=avs&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=berghahn&dataSource[]=cabi&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=du_press&dataSource[]=esa&dataSource[]=eu_press&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=ejtr&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imanager&dataSource[]=imedpub&dataSource[]=informa_healthcare&dataSource[]=informs&dataSource[]=iop&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=leftcoast&dataSource[]=lu_press&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=nature&dataSource[]=oxford&dataSource[]=pier_professional&dataSource[]=pnas&dataSource[]=portlandpress&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=rcn&dataSource[]=ria&dataSource[]=rsc&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer_journal&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=wiley&dataSource[]=pct
© 2012 DeepDyve, Inc. All rights reserved.
Terms of Service | Privacy Policy
