Abstract
Inflammatory bowel disease is a chronic, relapsing, and tissue-destructive disease. Resveratrol (3,4,5-trihydroxy-trans-stilbene), a naturally occurring polyphenol that exhibits beneficial pleiotropic health effects, is recognized as one of the most promising natural molecules in the prevention and treatment of chronic inflammatory disease and autoimmune disorders. In the present study, we investigated the effect of resveratrol on dextran sodium sulfate (DSS)-induced colitis in mice and found that it effectively attenuated overall clinical scores as well as various pathological markers of colitis. Resveratrol reversed the colitis-associated decrease in body weight and increased levels of serum amyloid A, tumor necrosis factor-α, interleukin (IL-6), and IL-1β. After resveratrol treatment, the percentage of CD4+ T cells in mesenteric lymph nodes (MLN) of colitis mice was restored to normal levels, and there was a decrease in these cells in the colon lamina propria (LP). Likewise, the percentages of macrophages in MLN and the LP of mice with colitis were decreased after resveratrol treatment. Resveratrol also suppressed cyclooxygenase-2 (COX-2) expression induced in DSS-exposed mice. Colitis was associated with a decrease in silent mating type information regulation-1 (SIRT1) gene expression and an increase in p-inhibitory κB expression and nuclear transcription factor-κB (NF-κB) activation. Resveratrol treatment of mice with colitis significantly reversed these changes. This study demonstrates for the first time that SIRT1 is involved in colitis, functioning as an inverse regulator of NF-κB activation and inflammation. Furthermore, our results indicate that resveratrol may protect against colitis through up-regulation of SIRT1 in immune cells in the colon.
Footnotes
This work was supported in part by the National Institutes of Health National Institute of Allergy and Infectious Diseases Extramural Activities [Grants IH-AI053703, AI058300]; the National Institutes of Health National Institute of Environmental Health Sciences [Grant ES09098]; the National Institutes of Health National Institute on Drug Abuse [Grant DA016545]; the National Institutes of Health National Heart, Lung, and Blood Institute [Grant HL058641]; and the National Institutes of Health National Center for Complementary and Alternative Medicine [Grant PO1-AT003961].
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.109.160838.
-
ABBREVIATIONS:
- IBD
- inflammatory bowel disease
- CD
- Crohn's disease
- IL
- interleukin
- TNF
- tumor necrosis factor
- RES
- resveratrol
- COX
- cyclooxygenase
- SIRT1
- silent information regulator-1
- NF-κB
- nuclear transcription factor κB
- IκB
- inhibitory κB
- Ab
- antibody
- DSS
- dextran sulfate sodium
- PBS
- phosphate-buffered saline
- MLN
- mesenteric lymph nodes
- LP
- lamina propria
- FACS
- fluorescence-activated cell sorter
- IFN-γ
- interferon γ
- ELISA
- enzyme-linked immunosorbent assay
- SAA
- serum amyloid A
- HRP
- horseradish peroxidase
- RT-PCR
- reverse transcription-polymerase chain reaction
- TNBS
- trinitrobenzenesulfonic acid.
- Received August 20, 2009.
- Accepted November 24, 2009.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|