title: Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6.
abstract: BACKGROUND
  The c-Jun N-terminal kinases (JNKs) are involved in signal transduction of inflammatory bowel diseases. The aim of this study was to examine the function of JNKs by using a low-dose dextran sulfate sodium (DSS) model in JNK1 knockout mice (Mapk8-/-), JNK2 knockout mice (Mapk9-/-), and wild-type controls (WT1, WT2).
  
  
  METHODS
  The animals were evaluated daily using a disease activity index. After 30 days, the intestine was evaluated histologically with a crypt damage score. CD4+ and CD8+ cells were quantified using immunofluorescence. Analysis of tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and transforming growth factor β1 (TGFB1) expression was carried out using LightCycler(®) real-time polymerase chain reaction.
  
  
  RESULTS
  Cyclic administration of low-dose DSS (1%) was not able to induce features of chronic colitis in Mapk8-/- WT2 mice. By contrast, DSS administration significantly increased the disease activity index in WT1 and Mapk9-/- mice. In Mapk9-/- mice, the crypt damage score and the number of CD4+ and CD8+ cells as features of chronic colitis/inflammation were also significantly elevated. Expression of TNFα, IL-6, and TGFB1 was not altered by the JNK knockout.
  
  
  CONCLUSIONS
  Administering DSS at a defined low concentration that is unable to induce colitis in WT animals leads to clinically and histologically detectable chronic colitis in Mapk9-/- mice. The reason for this disease-inducing effect resulting from the loss of JNK2 remains to be elucidated. Expression of TNFα, IL-6, and TGFB1 does not appear to be involved; proapoptotic JNK2 may prolong the activity of proinflammatory immune cells, leading to perpetuation of the inflammation.
authors: Department of General and Visceral Surgery, St Josef Hospital, Ruhr-University of Bochum, Bochum, Germany.
authors: Sabine
authors: S
authors: Kersting
authors: Kirstin
authors: K
authors: Reinecke
authors: Christoph
authors: C
authors: Hilgert
authors: Monika S
authors: MS
authors: Janot
authors: Elisabeth
authors: E
authors: Haarmann
authors: Martin
authors: M
authors: Albrecht
authors: Annette M
authors: AM
authors: Müller
authors: Thomas
authors: T
authors: Herdegen
authors: Ulrich
authors: U
authors: Mittelkötter
authors: Waldemar
authors: W
authors: Uhl
authors: Ansgar M
authors: AM
authors: Chromik
keywords: JNK knockout mice; T-cell immune response; inflammatory bowel diseases; proinflammatory cytokines