期刊论文详细信息
BMC Gastroenterology
Effects of Interleukin-4 or Interleukin-10 gene therapy on trinitrobenzenesulfonic acid-induced murine colitis
Si-De Liu1  Yang Bai1  Ji-De Wang1  Li-Hong Bi1  Ying-Hao Lin1  Jing Xiong1 
[1]Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
关键词: Gene therapy;    TNBS-induced colitis;    Interleukin-10;    Interleukin-4;    Inflammatory bowel disease;   
Others  :  856850
DOI  :  10.1186/1471-230X-13-165
 received in 2013-05-27, accepted in 2013-11-14,  发布年份 2013
PDF
【 摘 要 】

Background

Inflammatory bowel disease (IBD) is characterized by disturbance of pro-inflammatory cytokines and anti-inflammatory cytokines. Previous studies have demonstrated the effect of anti-inflammatory cytokines, such as interleukin-10 (IL-10) or IL-4 on IBD, but their data were controversial. This study further investigated the effect of IL-4 (IL-4), IL-10 and their combination on treatment of trinitrobenzenesulfonic acid (TNBS)-induced murine colitis.

Methods

pcDNA3.0 carrying murine IL-4 or IL-10 cDNA was encapsulated with LipofectAMINE 2000 and intraperitoneally injected into mice with TNBS-induced colitis. The levels of intestinal IL-4 and IL-10 mRNA were confirmed by quantitative-RT-PCR. Inflamed tissues were assessed by histology and expression of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and IL-6.

Results

The data confirmed that IL-4 or IL-10 over-expression was successfully induced in murine colon tissues after intraperitoneal injection. Injections of IL-4 or IL-10 significantly inhibited TNBS-induced colon tissue damage, disease activity index (DAI) and body weight loss compared to the control mice. Furthermore, expression of IFN-γ, TNF-α and IL-6 was markedly blocked by injections of IL-4 or IL-10 plasmid. However, there was less therapeutic effect in mice injected with the combination of IL-4 and IL-10.

Conclusions

These data suggest that intraperitoneal injection of IL-4 or IL-10 plasmid was a potential strategy in control of TNBS-induced murine colitis, but their combination had less effect.

【 授权许可】

   
2013 Xiong et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140723041052617.pdf 1307KB PDF download
57KB Image download
43KB Image download
79KB Image download
127KB Image download
61KB Image download
【 图 表 】

【 参考文献 】
  • [1]Engel MA, Neurath MF: New pathophysiological insights and modern treatment of IBD. J Gastroenterol 2010, 45:571-583.
  • [2]Ullman T, Odze R, Farraye FA: Diagnosis and management of dysplasia in patients with ulcerative colitis and Crohn’s disease of the colon. Inflamm Bowel Dis 2009, 15:630-638.
  • [3]Izzo AA, Camilleri M: Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects. Gut 2008, 57:1140-1155.
  • [4]Kappelman MD, Rifas-Shiman SL, Kleinman K, Ollendorf D, Bousvaros A, Grand RJ, Finkelstein JA: The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol 2007, 12:1424-1429.
  • [5]Triantafillidis JK, Nasioulas G, Kosmidis PA: Colorectal cancer and inflammatory bowel disease: epidemiology, risk factors, mechanisms of carcinogenesis and prevention strategies. Anticancer Res 2009, 29:2727-2737.
  • [6]Ahmadi A, Polyak S, Draganov PV: Colorectal cancer surveillance in inflammatory bowel disease: the search continues. World J Gastroenterol 2009, 15:61-66.
  • [7]Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, Kleinschek MA, Owyang A, Mattson J, Blumenschein W, Murphy E, Sathe M, Cua DJ, Kastelein RA, Rennick D: Interleukin-23 is essential for T cell-mediated colitis and promotes inflammation via interleukin-17 and interleukin 6. J Clin Invest 2006, 116:1310-1316.
  • [8]Maloy KJ, Kullberg MC: IL-23 and Th17 cytokines in intestinal homeostasis. Mucosal Immunol 2008, 1:339-349.
  • [9]Braat H, Peppelenbosch MP, Hommes DW: Interleukin-10-based therapy for inflammatory bowel disease. Expert Opin Biol Ther 2003, 3:725-731.
  • [10]Li MC, He SH: IL-10 and its related cytokines for treatment of inflammatory bowel disease. World J Gastroenterol 2004, 10:620-625.
  • [11]Williams LM, Ricchetti G, Sarma U, Smallie T, Foxwell BM: Interleukin-10 suppression of myeloid cell activation- a continuing puzzle. Immunology 2004, 113:281-292.
  • [12]Rennick DM, Fort MM: Lessons from genetically engineered animal models. XII. IL-10-deficient (IL-10(−/−) mice and intestinal inflammation. Am J Physiol Gastrointest Liver Physiol 2000, 278:G829-G833.
  • [13]Nakase H, Okazaki K, Tabata Y, Ozeki M, Watanabe N, Ohana M, Uose S, Uchida K, Nishi T, Mastuura M, Tamaki H, Itoh T, Kawanami C, Chiba T: New cytokine delivery system msing gelatin microspheres containing interleukin-10 for experimental inflammatory bowel disease. J Pharmacol Exp Ther 2002, 301:59-65.
  • [14]Lindsay J, Van Montfrans C, Brennan F, Van Deventer S, Drillenburg P, Hodgson H, Te Velde A, Sol Rodriguez Pena M: IL-10 gene therapy prevents TNBS-induced colitis. Gene Ther 2002, 9:1715-1721.
  • [15]Lindsay JO, Sandison A, Cohen P, Brennan FM, Hodgson HJ: IL-10 gene therapy is therapeutic for dextran sodium sulfate-induced murine colitis. Dig Dis Sci 2004, 49:1327-1334.
  • [16]Rogler G, Andus T: Cytokines in inflammatory bowel disease. World J Surg 1998, 22:382-389.
  • [17]Niessner M, Volk BA: Phenotypic and immunoregulatory analysis of intestinal T-cells in patients with inflammatory bowel disease: evaluation of an in vitro model. Eur J Clin Invest 1995, 25:155-164.
  • [18]Iijima H, Takahashi I, Kishi D, Kim JK, Kawano S, Hori M, Kiyono H: Alteration of interleukin 4 production results in the inhibition of T helper type 2 cell-dominated inflammatory bowel disease in T cell receptor alpha chaindeficient mice. J Exp Med 1999, 190:607-615.
  • [19]Khan MM, Chatterjee S, Dwivedi VP, Pandey NK, Singh Y, Tousif S, Bhavesh NS, Van Kaer L, Das J, Das G: CD4+ T cell-derived novel peptide Thp5 induces interleukin-4 production in CD4 + T Cells to direct T helper 2 cell differentiation. J Biol Chem 2012, 287:2830-2835.
  • [20]Karltunnen R, Breese EJ, Walker-Smith JA, MacDonald TT: Decreased mucosal interleukin-4 (IL-4) production in gut inflammation. J Clin Pathol 1994, 47:1015-1108.
  • [21]Stevceva L, Pavli P, Husband A, Ramsay A, Doe WF: Dextran sulphate sodium-induced colitis is ameliorated in interleukin 4 deficient mice. Genes Immunity 2001, 2:309-316.
  • [22]Wirtz S, Neufert C, Weigmann B, Weigmann B, Neurath MF: Chemically induced mouse models of intestinal inflammation. Nat Protoc 2007, 2:541-546.
  • [23]Schmid RM, Weidenbach H, Liptay S, Adler G: Direct gene transfer into the colon using a double-balloon catheter. Endoscopy 1997, 29:39-43.
  • [24]Chen J, Tian B, Yin X, Zhang Y, Hu D, Hu Z, Liu M, Pan Y, Zhao J, Li H, Hou C, Wang J, Zhang Y: Preparation, characterization and transfection efficiency of cationic PEGylated PLA nanoparticles as gene delivery systems. J Biotechnol 2007, 130:107-113.
  • [25]Wang D, Xu J, Feng Y, Liu Y, Mchenga SS, Shan F, Sasaki J, Lu C: Liposomal oral DNA vaccine (mycobacterium DNA) elicits immune response. Vaccine 2010, 28:3134-3142.
  • [26]Liptay S, Weidenbach H, Adler G, Schmid RM: Colon epithelium can be transiently transfected with liposomes, calcium phosphate precipitation and DEAE dextran in vivo. Digestion 1998, 59:142-147.
  • [27]Arenas RB, Fichera A, Mok P, Blanco MC, Michelassi F: Introduction of human adenomatous polyposis coli gene into Min mice via cationic liposomes. Surgery 1996, 120:712-717.
  • [28]Lee J, Hargest R, Wasan H, Phillips RK: Liposome-mediated adenomatous polyposis coli gene therapy: a novel anti-adenoma strategy in multiple intestinal neoplasia mouse model. Dis Colon Rectum 2004, 47:2105-2113.
  • [29]Chun S, Daheshia M, Lee S, Rouse BT: Immune modulation by IL-10 gene transfer via viral vector and plasmid DNA: implication for gene therapy. Cell Immunol 1999, 15:194-204.
  • [30]Zhang Y, Cristofaro P, Silbermann R, Pusch O, Boden D, Konkin T, Hovanesian V, Monfils PR, Resnick M, Moss SF, Ramratnam B: Engineering mucosal RNA interference in vivo. Mol Ther 2006, 14:336-342.
  • [31]Ganta VC, Cromer W, Mills GL, Traylor J, Jennings M, Daley S, Clark B, Mathis JM, Bernas M, Boktor M, Jordan P, Witte M, Alexander JS: Angiopoietin-2 in experimental colitis. Inflamm Bowel Dis 2010, 16:1029-1039.
  • [32]Neurath MF, Fuss I, Kelsall BL, Stüber E, Strober W: Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 1995, 182:1281-1290.
  • [33]Strober W, Fuss IJ, Blumberg RS: The immunology of mucosal models of inflammation. Annu Rev Immunol 2002, 20:495-549.
  • [34]Foligne B, Nutten S, Steidler L, Dennin V, Goudercourt D, Mercenier A, Pot B: Recommendations for improved use of the murine TNBS-induced colitis model in evaluating anti-inflammatory properties of lactic acid bacteria: technical and microbiological aspects. Dig Dis Sci 2006, 51:390-400.
  • [35]Barbara G, Xing Z, Hogaboam CM, Gauldie J, Collins SM: Interleukin 10 gene transfer prevents experimental colitis in rats. Gut 2000, 46:344-349.
  • [36]Lindsay JO, Ciesielski CJ, Scheinin T, Brennan FM, Hodgson HJ: Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis. Gut 2003, 52:363-369.
  • [37]Hogaboam CM, Vallance BA, Kumar A, Addison CL, Graham FL, Gauldie J, Collins SM: Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease. J Clin Invest 1997, 100:2766-2776.
  • [38]Fort MM, Lesley R, Davidson NJ: IL-4 exacerbates disease in a Th1 cell transfer model of colitis. J Immunol 2001, 166:2793-2800.
  • [39]Pastorelli L, Garg RR, Hoang SB, Spina L, Mattioli B, Scarpa M, Fiocchi C, Vecchi M, Pizarro TT: Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis. Proc Natl Acad Sci USA 2010, 107:8017-8022.
  • [40]Sanchez-Munoz F, Dominguez-Lopez A, Yamamoto-Furusho JK: Role of cytokines in inflammatory bowel disease. World J Gastroenterol 2008, 14:4280-4288.
  • [41]Mitsuyama K, Toyonaga A, Sasaki E, Ishida O, Ikeda H, Tsuruta O, Harada K, Tateishi H, Nishiyama T, Tanikawa K: Soluble interleukin-6 receptors in inflammatory bowel disease: relation to circulating interleukin-6. Gut 1995, 36:45-49.
  • [42]Reimund JM, Wittersheim C, Dumont S, Muller CD, Baumann R, Poindron P, Duclos B: Mucosal inflammatory cytokine production by intestinal biopsies in patients with ulcerative colitis and Crohn’s disease. J Clin Immunol 1996, 16:144-150.
  • [43]Li Y, de Haar C, Chen M, Deuring J, Gerrits MM, Smits R, Xia B, Kuipers EJ, van der Woude CJ: Disease-related expression of the IL6/STAT3/SOCS3 signalling pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis. Gut 2010, 59:227-235.
  • [44]Pasare C, Medzhitov R: Toll pathway-dependent blockade of CD4 + CD25+ T cell-mediated suppression by dendritic cells. Science 2003, 299:1033-1036.
  • [45]Briscoe DM, Cotran RS, Pober JS: Effects of tumor necrosis factor, lipopolysaccharide, and IL-4 on the expression of vascular cell adhesion molecule-i in vivo. Correlation with CD3 + T cell infiltration. J Immunol 1992, 149:2954-2960.
  • [46]Schleimer RP, Sterbinsky SA, Kaiser J, Bickel CA, Klunk DA, Tomioka K, Newman W, Luscinskas FW, Gimbrone MA Jr, McIntyre BW: IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. J Immunol 1992, 148:1086-1092.
  • [47]Phillips JO, Everson MP, Moldoveanu Z, Lue C, Mestecky J: Synergistic effect of IL-4 and IFN-y on the expression of polymeric Ig receptor (secretory component) and IgA binding by human epithelial cells. J Immunol 1990, 145:1740-1744.
  文献评价指标  
  下载次数:36次 浏览次数:28次