• 1
    Andus T, Gross V. Etiology and pathophysiology of inflammatory bowel disease − environmental factors. Hepatogastroenterology 2000; 47: 2943.
  • 2
    Sartor RB. Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases. Am J Gastroenterol 1997; 92: S511.
  • 3
    Brimnes J, Reimann J, Nissen M, Claesson M. Enteric bacterial antigens activate CD4 (+) T cells from scid mice with inflammatory bowel disease. Eur J Immunol 2001; 31: 2331.
  • 4
    Dianda L, Hanby AM, Wright NA, Sebesteny A, Hayday AC, Owen MJ. T cell receptor-alpha beta-deficient mice fail to develop colitis in the absence of a microbial environment. Am J Pathol 1997; 150: 917.
  • 5
    Madsen KL, Malfair D, Gray D, Doyle JS, Jewell LD, Fedorak RN. Interleukin-10 gene-deficient mice develop a primary intestinal permeability defect in response to enteric microflora. Inflamm Bowel Dis 1999; 5: 26270.
  • 6
    Schultz M, Tonkonogy SL, Sellon RK et al. IL-2-deficient mice raised under germfree conditions develop delayed mild focal intestinal inflammation. Am J Physiol 1999; 276: G1461G1472.
  • 7
    Veltkamp C, Tonkonogy SL, De Jong YP et al. Continuous stimulation by normal luminal bacteria is essential for the development and perpetuation of colitis in Tg (epsilon26) mice. Gastroenterology 2001; 120: 90013.
  • 8
    Sartor RB. Role of the enteric microflora in the pathogenesis of intestinal inflammation and arthritis [Review]. Aliment Pharmacol Ther 1997; 11: 1722.
  • 9
    Sartor RB. The influence of normal microbial flora on the development of chronic mucosal inflammation. Res Immunol 1997; 148: 56776.
  • 10
    Duggan AE, Usmani I, Neal KR, Logan RF. Appendicectomy, childhood hygiene, Helicobacter pylori status, and risk of inflammatory bowel disease: a case–control study. Gut 1998; 43: 4948.
  • 11
    Gent AE, Hellier MD, Grace RH, Swarbrick ET, Coggon D. Inflammatory bowel disease and domestic hygiene in infancy. Lancet 1994; 343: 7667.
  • 12
    Ogura Y, Bonen DK, Inohara N et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 2001; 411: 6036.
  • 13
    Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem 2001; 276: 48128.
  • 14
    Krieg AM. Now I know my CpGs. Trends Microbiol 2001; 9: 24952.
  • 15
    Krieg AM, Yi AK, Matson S et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995; 374: 5469.
  • 16
    Krieg AM. Immune effects and mechanisms of action of CpG motifs. Vaccine 2000; 19: 61822.
  • 17
    Burge C, Campbell AM, Karlin S. Over- and under-representation of short oligonucleotides in DNA sequences. Proc Natl Acad Sci USA 1992; 89: 135862.
  • 18
    Hemmi H, Takeuchi O, Kawai T et al. A toll-like receptor recognizes bacterial DNA. Nature 2000; 408: 7405.
  • 19
    O'Hagan DT, MacKichan ML, Singh M. Recent developments in adjuvants for vaccines against infectious diseases. Biomol Eng 2001; 18: 6985.
  • 20
    Krieg AM. From bugs to drugs: therapeutic immunomodulation with oligodeoxynucleotides containing CpG sequences from bacterial DNA. Antisense Nucl Acid Drug Dev 2001; 11: 1818.
  • 21
    Metzger WJ, Nyce JW. Oligonucleotide therapy of allergic asthma. J Allergy Clin Immunol 1999; 104: 2606.
  • 22
    Obermeier F, Dunger N, Deml L, Herfarth H, Schölmerich J, Falk W. CpG motifs of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice. Eur J Immunol 2002; 32: 208492.
  • 23
    Sparwasser T, Koch ES, Vabulas RM et al. Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells. Eur J Immunol 1998; 28: 204554.
  • 24
    Obermeier F, Kojouharoff G, Hans W, Schölmerich J, Gross V, Falk W. Interferon-gamma (IFN-gamma)- and tumour necrosis factor (TNF)-induced nitric oxide as toxic effector molecule in chronic dextran sulphate sodium (DSS)-induced colitis in mice. Clin Exp Immunol 1999; 116: 23845.
  • 25
    Alves-Rosa F, Beigier-Bompadre M, Fernandez G et al. Tolerance to lipopolysaccharide (LPS) regulates the endotoxin effects on Shiga toxin-2 lethality. Immunol Lett 2001; 76: 12531.
  • 26
    Alves-Rosa F, Vulcano M, Beigier-Bompadre M, Fernandez G, Palermo M, Isturiz MA. Interleukin-1beta induces in vivo tolerance to lipopolysaccharide in mice. Clin Exp Immunol 2002; 128: 2218.
  • 27
    Bundschuh DS, Barsig J, Hartung T et al. Granulocyte-macrophage colony-stimulating factor and IFN-gamma restore the systemic TNF-alpha response to endotoxin in lipopolysaccharide-desensitized mice. J Immunol 1997; 158: 286271.
  • 28
    Steidler L, Hans W, Schotte L et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 2000; 289: 13525.
  • 29
    Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 2002; 20: 70960.
  • 30
    Kobayashi H, Horner AA, Takabayashi K et al. Immunostimulatory DNA pre-priming: a novel approach for prolonged Th1-biased immunity. Cell Immunol 1999; 198: 6975.
  • 31
    Krieg AM. The role of CpG motifs in innate immunity. Curr Opin Immunol 2000; 12: 3543.
  • 32
    Hans W, Scholmerich J, Gross V, Falk W. Interleukin-12 induced interferon-gamma increases inflammation in acute dextran sulfate sodium induced colitis in mice. Eur Cytokine Netw 2000; 11: 6774.
  • 33
    Rachmilewitz D, Karmeli F, Takabayashi K et al. Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis. Gastroenterology 2002; 122: 142841.
  • 34
    Medvedev AE, Henneke P, Schromm A et al. Induction of tolerance to lipopolysaccharide and mycobacterial components in Chinese hamster ovary/CD14 cells is not affected by overexpression of toll-like receptors 2 or 4. J Immunol 2001; 167: 225767.
  • 35
    Lehner MD, Morath S, Michelsen KS, Schumann RR, Hartung T. Induction of cross-tolerance by lipopolysaccharide and highly purified lipoteichoic acid via different toll-like receptors independent of paracrine mediators. J Immunol 2001; 166: 51617.
  • 36
    Yeo SJ, Yoon JG, Hong SC, Yi AK. CpG DNA induces self- and cross-hyporesponsiveness of RAW264.7 cells in response to CpG DNA and lipopolysaccharide: alterations in IL-1 receptor-associated kinase expression. J Immunol 2003; 170: 105261.
  • 37
    Quintana FJ, Rotem A, Carmi P, Cohen IR. Vaccination with empty plasmid DNA or CpG oligonucleotide inhibits diabetes in nonobese diabetic mice: modulation of spontaneous 60-kDa heat shock protein autoimmunity. J Immunol 2000; 165: 614855.
  • 38
    Mottet C, Uhlig HH, Powrie F. Cutting edge: cure of colitis by CD4 (+) CD25 (+) regulatory T cells. J Immunol 2003; 170: 393943.
  • 39
    Groux H, O'Garra A, Bigler M et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997; 389: 73742.
  • 40
    Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J Exp Med 2003; 197: 40311.
  • 41
    Bradbury J. New treatment for inflammatory bowel disease could soon enter clinical trials. Lancet 2002; 359: 1583.