PMID- 19940103 OWN - NLM STAT- MEDLINE DCOM- 20100413 LR - 20211020 IS - 1521-0103 (Electronic) IS - 0022-3565 (Print) IS - 0022-3565 (Linking) VI - 332 IP - 3 DP - 2010 Mar TI - Resveratrol (trans-3,5,4'-trihydroxystilbene) induces silent mating type information regulation-1 and down-regulates nuclear transcription factor-kappaB activation to abrogate dextran sulfate sodium-induced colitis. PG - 829-39 LID - 10.1124/jpet.109.160838 [doi] AB - 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-alpha, interleukin (IL-6), and IL-1beta. 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 kappaB expression and nuclear transcription factor-kappaB (NF-kappaB) 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-kappaB activation and inflammation. Furthermore, our results indicate that resveratrol may protect against colitis through up-regulation of SIRT1 in immune cells in the colon. FAU - Singh, Udai P AU - Singh UP AD - Department of Pathology, School of Medicine, University of South Carolina, Columbia, SC 29208, USA. FAU - Singh, Narendra P AU - Singh NP FAU - Singh, Balwan AU - Singh B FAU - Hofseth, Lorne J AU - Hofseth LJ FAU - Price, Robert L AU - Price RL FAU - Nagarkatti, Mitzi AU - Nagarkatti M FAU - Nagarkatti, Prakash S AU - Nagarkatti PS LA - eng GR - DA016545/DA/NIDA NIH HHS/United States GR - P01-AT003961/AT/NCCIH NIH HHS/United States GR - P01 AT003961/AT/NCCIH NIH HHS/United States GR - R01 HL058641/HL/NHLBI NIH HHS/United States GR - R01 DA016545/DA/NIDA NIH HHS/United States GR - ES09098/ES/NIEHS NIH HHS/United States GR - R01 AI053703/AI/NIAID NIH HHS/United States GR - R01 AI058300/AI/NIAID NIH HHS/United States GR - HL058641/HL/NHLBI NIH HHS/United States GR - IH-AI053703/AI/NIAID NIH HHS/United States GR - AI058300/AI/NIAID NIH HHS/United States GR - R01 ES009098/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20091125 PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 0 (Stilbenes) RN - 9042-14-2 (Dextran Sulfate) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 3.5.1.- (Sirt1 protein, mouse) RN - EC 3.5.1.- (Sirtuin 1) RN - Q369O8926L (Resveratrol) SB - IM MH - Administration, Oral MH - Animals MH - CD4 Lymphocyte Count MH - Colitis/chemically induced/metabolism/*prevention & control MH - Colon/drug effects/metabolism/pathology MH - Cyclooxygenase 2/biosynthesis MH - Cytokines/blood MH - *Dextran Sulfate MH - Down-Regulation MH - Female MH - Intestinal Mucosa/immunology/pathology MH - Lymph Nodes/immunology/pathology MH - Macrophages/immunology/pathology MH - Mesentery MH - Mice MH - Mice, Inbred C57BL MH - Mucous Membrane/immunology/pathology MH - NF-kappa B/*biosynthesis MH - Resveratrol MH - Sirtuin 1/*biosynthesis MH - Stilbenes/administration & dosage/*pharmacology/therapeutic use PMC - PMC2835444 EDAT- 2009/11/27 06:00 MHDA- 2010/04/14 06:00 PMCR- 2011/03/01 CRDT- 2009/11/27 06:00 PHST- 2009/11/27 06:00 [entrez] PHST- 2009/11/27 06:00 [pubmed] PHST- 2010/04/14 06:00 [medline] PHST- 2011/03/01 00:00 [pmc-release] AID - jpet.109.160838 [pii] AID - 3557518 [pii] AID - 10.1124/jpet.109.160838 [doi] PST - ppublish SO - J Pharmacol Exp Ther. 2010 Mar;332(3):829-39. doi: 10.1124/jpet.109.160838. Epub 2009 Nov 25.