The incidence of allergic diseases such as atopic dermatitis (AD) has been dramatically increasing in the US and other industrialized countries for the past two decades. We and others have demonstrated that Tec family protein-tyrosine kinases have crucial roles in the activation of immune cells elicited by the engagement of antigen receptors or Fc receptors. As such, these kinases are supposed to play critical roles in the pathogenesis of AD and other allergic diseases that involve the activation of T and B lymphocytes, mast cells, and eosinophils. We recently identified a small-molecule compound, terreic acid (TA), as a selective inhibitor of Tec family kinases. In addition, we recently established highly efficient experimental conditions to rapidly induce skin lesions in AD-prone NC/Nga mice. Using this mouse model, we propose to explore whether TA or related compounds are therapeutically efficacious as a treatment of AD. Since we have a screening method for searching for Tec inhibitors whose usefulness has been proven, we will also expand our search for better compounds.
| Kawakami, Yuko; Yumoto, Kenji; Kawakami, Toshiaki (2007) An improved mouse model of atopic dermatitis and suppression of skin lesions by an inhibitor of Tec family kinases. Allergol Int 56:403-9 |
| Kawakami, Yuko; Inagaki, Naoki; Salek-Ardakani, Shahram et al. (2006) Regulation of dendritic cell maturation and function by Bruton's tyrosine kinase via IL-10 and Stat3. Proc Natl Acad Sci U S A 103:153-8 |
