PMID- 20885979 OWN - NLM STAT- MEDLINE DCOM- 20110218 LR - 20211020 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 5 IP - 9 DP - 2010 Sep 24 TI - Curcumin protects intestinal mucosal barrier function of rat enteritis via activation of MKP-1 and attenuation of p38 and NF-kappaB activation. PG - e12969 LID - e12969 [pii] LID - 10.1371/journal.pone.0012969 [doi] AB - BACKGROUND: Intestinal mucosa barrier (IMB) dysfunction results in many notorious diseases for which there are currently few effective treatments. We studied curcumin's protective effect on IMB and examined its mechanism by using methotrexate (MTX) induced rat enteritis model and lipopolysaccharide (LPS) treated cell death model. METHODOLOGY/PRINCIPAL FINDINGS: Curcumin was intragastrically administrated from the first day, models were made for 7 days. Cells were treated with curcumin for 30 min before exposure to LPS. Rat intestinal mucosa was collected for evaluation of pathological changes. We detected the activities of D-lactate and diamine oxidase (DAO) according to previous research and measured the levels of myeloperoxidase (MPO) and superoxide dismutase (SOD) by colorimetric method. Intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) were determined by RT-PCR and IL-10 production was determined by ELISA. We found Curcumin decreased the levels of D-lactate, DAO, MPO, ICAM-1, IL-1beta and TNF-alpha, but increased the levels of IL-10 and SOD in rat models. We further confirmed mitogen-activated protein kinase phosphatase-1 (MKP-1) was activated but phospho-p38 was inhibited by curcumin by western blot assay. Finally, NF-kappaB translocation was monitored by immunofluorescent staining. We showed that curcumin repressed I-kappaB and interfered with the translocation of NF-kappaB into nucleus. CONCLUSIONS/SIGNIFICANCE: The effect of curcumin is mediated by the MKP-1-dependent inactivation of p38 and inhibition of NF-kappaB-mediated transcription. Curcumin, with anti-inflammatory and anti-oxidant activities may be used as an effective reagent for protecting intestinal mucosa barrier and other related intestinal diseases. FAU - Song, Wei-Bing AU - Song WB AD - Department of Gerontology, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, China. songweibing@yahoo.com FAU - Wang, Yuan-Yuan AU - Wang YY FAU - Meng, Fan-Su AU - Meng FS FAU - Zhang, Qing-Hua AU - Zhang QH FAU - Zeng, Jian-Ying AU - Zeng JY FAU - Xiao, Li-Ping AU - Xiao LP FAU - Yu, Xin-Pei AU - Yu XP FAU - Peng, Dan-dan AU - Peng DD FAU - Su, Lei AU - Su L FAU - Xiao, Bing AU - Xiao B FAU - Zhang, Zhen-Shu AU - Zhang ZS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100924 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (NF-kappa B) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.1.3.48 (Dual Specificity Phosphatase 1) RN - EC 3.1.3.48 (Dusp1 protein, rat) RN - IT942ZTH98 (Curcumin) SB - IM MH - Animals MH - Cell Line MH - Curcumin/*administration & dosage MH - Disease Models, Animal MH - Dual Specificity Phosphatase 1/genetics/*metabolism MH - Enteritis/*drug therapy/enzymology/genetics/metabolism MH - Enzyme Activation/drug effects MH - Gene Expression Regulation/drug effects MH - Humans MH - Intercellular Adhesion Molecule-1/genetics/metabolism MH - Intestinal Mucosa/*drug effects/enzymology/metabolism MH - Mice MH - NF-kappa B/genetics/*metabolism MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - p38 Mitogen-Activated Protein Kinases/genetics/*metabolism PMC - PMC2945766 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2010/10/05 06:00 MHDA- 2011/02/22 06:00 PMCR- 2010/09/24 CRDT- 2010/10/02 06:00 PHST- 2010/07/08 00:00 [received] PHST- 2010/09/01 00:00 [accepted] PHST- 2010/10/02 06:00 [entrez] PHST- 2010/10/05 06:00 [pubmed] PHST- 2011/02/22 06:00 [medline] PHST- 2010/09/24 00:00 [pmc-release] AID - e12969 [pii] AID - 10-PONE-RA-20838R1 [pii] AID - 10.1371/journal.pone.0012969 [doi] PST - epublish SO - PLoS One. 2010 Sep 24;5(9):e12969. doi: 10.1371/journal.pone.0012969.