International Journal of Colorectal Disease

, Volume 17, Issue 4, pp 223–232

Abrogated lymphocyte infiltration and lowered CD14 in dextran sulfate induced colitis in mice treated with p65 antisense oligonucleotides

  • Ann-Kristin Spiik
  • Anna Ridderstad
  • Lars-Göran Axelsson
  • Tore Midtvedt
  • Lars Björk
  • Sven Pettersson
Original Article

DOI: 10.1007/s00384-001-0366-3

Cite this article as:
Spiik, A., Ridderstad, A., Axelsson, L. et al. Int J Colorectal Dis (2002) 17: 223. doi:10.1007/s00384-001-0366-3

Abstract.

Background and aims: Dextran sulfate sodium (DSS) induced colitis exhibits a predominantly NF-κB dependent proinflammatory cytokine profile and shares similarities with human inflammatory bowel disease (IBD). Lamina propria macrophages of IBD patients display elevated levels of NF-κB p65. Knowing the role of NF-κB in IBD, we investigated the beneficial cellular mechanisms underlying the lasting effect of a single p65 antisense treatment in DSS-colitis mice. Methods: One local dose of p65 antisense oligonucleotides was administered in DSS colitis mice. Ten days later the mice were killed and examined at cellular and biochemical levels. The level of p65 in lamina propria cells was determined by electrophoretic mobility shift assay and by intracellular immunofluorescent staining of nuclear p65 levels, using laser scanning cytometer. Results: FACS analysis demonstrated a considerable drop in infiltrating lymphocytes and a drastic reduction in CD14+ cells in mice treated with p65 antisense oligonucleotides. Moreover, abrogation of inflammation extended all the way to the cecum in treated mice. Treatment was correlated with decreased DNA binding activity of NF-κB. Conclusions: Our data strongly support a model in which p65 antisense treatment possesses the capacity to disrupt the pathogenic autocrine loop propagated by NF-κB at the chronic phase of IBD.

Inflammatory bowel disease Lamina propria mononuclear cells Antisense oligonucleotides Nuclear factor κB CD14

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Ann-Kristin Spiik
    • 1
  • Anna Ridderstad
    • 1
  • Lars-Göran Axelsson
    • 2
  • Tore Midtvedt
    • 2
  • Lars Björk
    • 4
  • Sven Pettersson
    • 1
  1. 1.Microbiology and Tumor Biology Center, Karolinska Institutet, Theorells väg 3, 17177 Stockholm, Sweden
  2. 2.Department of Gastroenterology and Hepatology, Karolinska Hospital, Stockholm, Sweden
  3. 3.Laboratory of Medical Microbial Ecology, Karolinska Institutet, Stockholm, Sweden
  4. 4.Biochemistry and Cell Biology Section, Pharmacia, Stockholm, Sweden