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Published on: December 19, 2019

Reduced oxazolone-induced skin inflammation in MAPKAP kinase 2 knockout mice

Anne T Funding1, Claus Johansen, Matthias Gaestel

  • 1Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.

The Journal of Investigative Dermatology
|November 7, 2008
PubMed

Insights

Mitogen-activated protein kinase 2 (MK2) plays a key role in skin inflammation. Inhibiting MK2 or its upstream activator p38 MAPK reduces inflammatory responses in a mouse model of allergic contact dermatitis.

Area of Science:

  • Immunology
  • Dermatology
  • Molecular Biology

Background:

  • Mitogen-activated protein kinase (MAPK) activated protein kinase 2 (MK2) is activated by p38 MAPK.
  • MK2 regulates proinflammatory cytokines, and its activation is observed in psoriatic epidermis.
  • The role of MK2 in skin inflammation is not well understood.

Purpose of the Study:

  • To investigate the role of MK2 in skin inflammation.
  • To examine MK2 activation in oxazolone-induced acute allergic contact dermatitis (ACD) in mice.

Main Methods:

  • Mice were sensitized and challenged with oxazolone to induce ACD.
  • Expression and activation of p38 MAPK and MK2 were analyzed.
  • Inflammatory response was assessed by ear thickness, myeloperoxidase activity, and histology.
  • The effect of p38 MAPK inhibitor SB202190 and MK2 knockout (KO) was evaluated.

Main Results:

  • Oxazolone treatment increased p38 MAPK and MK2 expression and activation.
  • SB202190 and MK2 deficiency significantly inhibited the inflammatory response.
  • MK2 KO mice showed decreased expression of IL-1beta, TNF-alpha, and IFN-gamma compared to wild-type mice.

Conclusions:

  • MK2 is activated during acute allergic contact dermatitis.
  • MK2 is a critical mediator of skin inflammation.
  • MK2 represents a potential therapeutic target for inflammatory skin diseases.

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