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Digestive Diseases and Sciences

, Volume 50, Issue 12, pp 2366–2378 | Cite as

NF-κB Activation Precedes Increases in mRNA Encoding Neurokinin-1 Receptor, Proinflammatory Cytokines, and Adhesion Molecules in Dextran Sulfate Sodium–Induced Colitis in Rats

  • Karen L. Reed
  • A. Brent Fruin
  • Adam C. Gower
  • Kelly D. Gonzales
  • Arthur F. Stucchi
  • Christopher D. Andry
  • Michael O'brien
  • James M Becker
Article

Abstract

Nuclear factor kappa B (NF-κ B) plays a key role in initiating inflammation associated with colitis. A systematic study was conducted in the rat DSS colitis model to determine the temporal relationship between NF-κ B activation and expression of substance P (SP), neurokinin-1 receptor (NK-1R), proinflammatory cytokines, and adhesion molecules. Rats were given 5% DSS in their water and sacrificed daily for 6 days. Colon tissue was collected for assessment of histological changes, NF-κ B activation, myeloperoxidase (MPO) activity, and expression of NK-1R, SP, TNFα, IL-1β, VCAM-1, ICAM-1, E-selectin, CINC-1, MIP-1α, and iNOS. NF-κ B activation increased, biphasically, on Day 1 and again on Days 4–6. The mRNA levels for ICAM-1, CINC-1, IL-1β, TNFα, VCAM-1, and NK-1R rose significantly (P< 0.05) by 2–4 days. Increased iNOS mRNA levels, MPO activity, and mucosal damage occurred on Day 6. These data demonstrate that NF-κ B activation substantially precedes the onset of physical disease signs and active inflammation.

KeyWords

ulcerative colitis NF-κb inflammation substance p neurokinin 1 receptor cytokines 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Karen L. Reed
    • 1
  • A. Brent Fruin
    • 1
  • Adam C. Gower
    • 1
  • Kelly D. Gonzales
    • 1
  • Arthur F. Stucchi
    • 1
  • Christopher D. Andry
    • 2
  • Michael O'brien
    • 2
  • James M Becker
    • 1
    • 3
  1. 1.Department of SurgeryBoston University School of MedicineBostonUSA
  2. 2.Department of PathologyBoston University School of MedicineBostonUSA
  3. 3.Department of SurgeryBoston University School of MedicineBostonUSA

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