کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10904032 | 1086553 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Redox regulation of MMP-3/TIMP-1 ratio in intestinal myofibroblasts: Effect of N-acetylcysteine and curcumin
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کلمات کلیدی
NF-kBExtracellular-regulated kinasesGSH/GSSG ratioMMP-3TIMPsBSOAP-1IBDECMNACGSHMmpsJnkc-Jun N-terminal kinases - C-Jun N-terminal kinasesERK1/2 - ERK1 / 2MAPKs - MAPK هاMitogen activated protein kinases - Mitogen فعال پروتئین کینازN-acetylcysteine - N-استیل سیستئینbuthionine sulfoximine - بوته یون سولفسیمیمCrohn׳s disease - بیماری کرونInflammatory bowel disease - بیماریهای التهابی رودهOxidative state - حالت اکسیداتیوtumor necrosis factor - فاکتور نکروز تومورNuclear factor-kB - فاکتور هسته ای kBExtracellular matrix - ماتریکس خارج سلولیMatrix metalloproteinases - متالوپروتئیناز ماتریکسTissue inhibitors of metalloproteinases - مهارکننده های متالوپروتئیناز بافتCurcumin - کورکومینGlutathione - گلوتاتیون
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Matrix metalloproteinases (MMPs) play a critical role in inflammation and ulcerations in gut of Crohn׳s disease (CD) patients. Intestinal subepithelial myofibroblasts (ISEMFs) secrete MMPs in response to inflammatory stimuli. Previous data showed in CD-ISEMFs increased oxidative status. The aim of this study was to investigate the role of ISEMFs in modulating the production of MMP-3 and TIMP-1, an inhibitor of MMPs activity. A relationship among oxidative stress, activity of antioxidants and MMP-3/TIMP-1 was also studied. ISEMFs isolated from CD patient colon and human colonic cell line of myofibroblasts (18Co) were used. Oxidative state was modulated by buthionine sulfoximine, an inhibitor of glutathione (GSH) synthesis, and N-acetylcysteine (NAC), GSH precursor. An up-regulation of MMP-3 due to increased oxidative state was found in CD-ISEMFs. Stimulation by tumor necrosis factor (TNF)α increased further MMP-3 levels. On the contrary, no change in TIMP-1 production was determined. NAC treatment decreased MMP-3 production in CD-ISMEFs and removed the enhancement due to TNFα. Similar effects were observed in 18Co cells treated with curcumin, antioxidant with anti-inflammatory properties. The involvement of MAPKs on MMP-3 redox regulation was also shown. This study demonstrates the involvement of ISEMFs and high oxidative state in the increased MMP-3 production found in intestinal mucosa of CD patients. NAC and curcumin normalize MMP-3 levels mainly in TNFα stimulated cells. A modulation of MMP-3 production by NAC and curcumin due to their direct action on transcriptional factors has been also suggested. Therefore, they could have a therapeutic use for the prevention and treatment of fistulaes in CD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 323, Issue 1, 15 April 2014, Pages 77-86
Journal: Experimental Cell Research - Volume 323, Issue 1, 15 April 2014, Pages 77-86
نویسندگان
Filippo Fontani, Tommaso Marcucci, Lucia Picariello, Francesco Tonelli, Maria Teresa Vincenzini, Teresa Iantomasi,