title: Targeting Pim1 kinase in the treatment of peanut allergy.
abstract: BACKGROUND
  Peanut sensitization is the most significant food allergen associated with life-threatening allergic reactions. Unlike many food sensitivities, peanut allergy often persists into adulthood. Presently, the only effective therapy is peanut avoidance. Effective preventative therapy requires an understanding of the pathways that lead to anaphylaxis. IgE and mast cell activation are essential contributors. The responsible pathways upstream are driven by pro-allergic T helper 2 differentiation and release of cytokines including interleukin-4 (IL-4) and IL-13.
  
  
  METHODS
  The research utilized an experimental model of peanut-induced anaphylaxis in mice that mimics many of the responses seen in the human disease. Following peanut sensitization and challenge, clinical responses, intestinal inflammatory and immune cell interactions, and genetic and molecular events were monitored. For the first time, evidence for Pim1 kinase involvement was demonstrated in association with the downregulation of Runx3, a known silencer of the IL-4 gene locus. Evidence for Pim1 kinase involvement was shown through the use of a small molecule inhibitor of Pim1 kinase.
  
  
  CONCLUSIONS
  Activation of Pim1 kinase and downregulation of Runx3 were essential to the development of peanut-induced intestinal anaphylaxis. Targeting of this Pim1 kinase-Runx3 axis may provide new therapeutic options in the prevention of life-threatening reactions to peanut.
authors.affiliation: National Jewish Health, Division of Cell Biology, Department of Pediatrics , 1400 Jackson Street, Denver, CO 80206 , USA +1 303 398 1196 ; +1 303 270 2105 ; gelfande@njhealth.org.
authors.forename: Meiqin
authors.initials: M
authors.lastname: Wang
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000818:Animals; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism*; D005656:Fungal Proteins; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D021183:Peanut Hypersensitivity / Q000378:metabolism* / Q000628:therapy
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D005656:Fungal Proteins; D020928:Mitogen-Activated Protein Kinases; C432694:Pim1 protein, Pichia pastoris