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| 1 | CTGF, intestinal stellate cells and carcinoid fi brogenesis显示文摘AIM: To investigate the role of small intestinal carcinoid tumor-derived fibrotic mediators, TGFβ1 and CTGF, in the mediation of fi brosis via activation of an 'intestinal' stellate cell. METHODS: GI carcinoid tumors were collected for Q RT-PCR analysis of CTGF and TGFβ1. Markers of stellate cell desmoplasia were identified in peritoneal fibrosis by immunohistochemistry and stellate cells cultured from fresh resected fibrotic tissue. CTGF and TGFβ1 were evaluated using quantitative tissue array profi ling (AQUA analysis) in a GI carcinoid tissue microarray (TMA) with immunostaining and correlated with clinical and histologically documented fi brosis. Serum CTGF was analyzed using a sandwich ELISA assay. RESULTS: Message levels of both CTGF and TGFβ1 in SI carcinoid tumors were signifi cantly increased (> 2-fold, P < 0.05) versus normal mucosa and gastric (non-f ibrotic) carcinoids. Activated stellate cells and markers of stellate cell-mediated fi brosis (vimentin, desmin) were identifi ed in histological fibrosis. An intestinal stellate cell was immunocytochemically and biochemically characterized and its TGFβ1 (10-7M) initiated CTGF transcription response (> 3-fold, P < 0.05) demonstrated. In SI carcinoid tumor patients with documented fi brosis, TMA analysis demonstrated higher CTGF immunostaining (AQUA Score: 92 ± 8; P <0.05), as well as elevated TGFβ1 (90.6 ± 4.4, P < 0.05). Plasma CTGF (normal 12.5 ± 2.6 ng/mL) was increased in SI carcinoid tumor patients (31 ± 10 ng/mL, P < 0.05) compared to non-fi brotic GI carcinoids (< 15 ng/mL).CONCLUSION: SI carcinoid tumor fibrosis is a CTGF/ TGFβ1-mediated stellate cell-driven fibrotic response. The delineation of the biology of fibrosis will facilitate diagnosis and enable development of agents to obviate its local and systemic complications. | M Kidd IM Modlin MD Shapiro RL Camp SM Mane W Usinger JR Murren | 2007 | World Journal of Gastroenterology2007，13，39： | 5 |
| 2 | Control of Mycobacterium tubercu- losis through mammalian Toll-like receptors 显示文摘 | Stenger S Modlin RL | 2002 | Curr Opin Immuno12002，14，4： | 1 |
| 3 | CTL-me- diated killing of intracellular Mycobacterium tubercu- losis is independent of target cell nuclear apoptosis 显示文摘 | Thoma-Uszynski S Stenger S Modlin RL | 2000 | J Immunol2000，165，10： | 1 |
| 4 | Cytotoxic T cell responses to intracellular pathogens显示文摘 | Stenger S Modlin RL | 1998 | Curr Opin Immunol1998，10，4： | 1 |
| 5 | The role of toll-like receptors in the pathogenesis and treatment of dermatological disease显示文摘 | McInturff JE Modlin RL Kim J | 2005 | J Invest Dermatol2005，125，1： | 1 |
| 6 | The role of Toll-like receptors in host defense against microbial infection 显示文摘 | Sieling PA Modlin RL | 2001 | Curr Opin Immunol2001，13，1： | 1 |
| 7 | Host Defense Mechanisms Triggered by Microbial Lipoproteins Through Toll-Like Receptors显示文摘 | Brightbill HD Libraty DH Krutzik SR Yang RB Belisle JT Bleharski JR Maitland M Norgard MV Plevy SE Smale ST Brennan PJ Bloom BR Godowski PJ Modlin RL | 1999 | Science1999，285，5428： | 1 |
| 8 | The toll of innate immunity on microbial pathogens 显示文摘 | Modlin RL Brightbill HD Godowski PJ | 1999 | N Engl J Med1999，340，23： | 1 |
| 9 | Local expression of anti-inflammatory cytokines in cancer显示文摘 | Yamamura M Modlin RL Ohmen JD | 1993 | J Clin Invest1993，91，3： | 1 |
| 10 | Toll-like receptor triggering of a vitamin D-media- ted human antimicrobial response 显示文摘 | Liu PT Stenger S Li H Wenzel L Tan BH Krutzik SR Ochoa MT Schauber J Wu K Meinken C Kamen DL Wagner M Bals R Steinmeyer A Ztigel U Gallo RL Eis- enberg D Hewison M Hollis BW Adams JS Bloom BR Modlin RL | 2006 | Science2006，311，： | 1 |
| 11 | The CD1 system: antigenpresenting molecules for T cell recognition of lipids and glycolipids 显示文摘 | Porcelli SA Modlin RL | 1999 | Annu Rev Immunol1999，17，： | 1 |
| 12 | Toll-like receptors: mammalian 'taste receptors' for a smorgasbord of microbial invaders显示文摘 | Modlin RL | 2002 | Curr Opin Microbiol2002，5，1： | 1 |
| 13 | Local expression of antiinflammatory cytokines in cancer显示文摘 | Yamamura M Modlin RL Ohmen JD | 1993 | J Clin Invest1993，91，3： | 1 |
| 14 | Mammalian toll-like receptors显示文摘 | Modlin RL | 2002 | Ann Allergy Asthma Immunol2002，88，6： | 1 |
| 15 | Mouse CD1 is mainly expressed on hemopoietic-derived cells 显示文摘 | Brossay L Jullien D Cardell S Sydora BC Burdin N Modlin RL Kronenberg M | 1997 | J Imrnunol1997，159，3： | 1 |
| 16 | The role of toll-like receptors in the pathogenesis and treatment of dermatological disease显示文摘 | MCINTURFF JE MODLIN RL KIM J | 2005 | J Invest Dermatol2005，125，1： | 1 |
| 17 | Role of toll-like receptors in response to bacterial infection显示文摘 | Hertz CJ Modlin RL | 2003 | Contrib Microbiol2003，10，： | 1 |
| 18 | Local expression of antiinflammatory cytokines in eancer显示文摘 | Yamamura M Modlin RL Ohemen JD | 1993 | J Clin Invest1993，91，3： | 1 |
| 19 | A Toll for DNA vaccines显示文摘 | | 2000 | Nature2000，408，： | 1 |
| 20 | Type 2 cytok- ines and negative immune regulation in human infections显示文摘 | Modlin RL Nutman TB | 1993 | Curr Opin Immunol1993，5，4： | 1 |
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