Abstract 69: Possible Involvement Of Proline-rich Tyrosine Kinase 2 (pyk2) In The Pathogenesis Of Kawasaki Disease
Introduction: Although etiology of Kawasaki disease (KD) remains elusive, a line of recent experimental studies implies that some kinds of infectious stimuli are implicate in the vasculitis through uncontrolled innate immune systems such as pattern recognition receptor (PPR)-mediated inflammatory signaling. It has already known that Candida albicans water-soluble fraction (CAWS) inducing KD-like vasculitis in mice function through PRP. Furthermore, it is reported that proline-rich tyrosine kinase (Pyk2), which is molecule involved in the PRPs-dependent signaling pathways, plays an important role in activation of NF-κB. Therefore, we investigated a possible relevance of Pyk2 in the pathogenesis of KD.
Methods: Pyk2-knock out (Pyk2-KO) and wild-type C57BL/6 mice (WT) were administered CAWS to induce KD-like vasculitis. Extension of the experimental vasculitis was immunohistochemically determined with anti-MPO antibody. CAWS-stimulated NF-κB activation was evaluated by quantifying nuclear translocation of NF-κB p65 subunit in peritoneal macrophages isolated from PYK2-KO and wild-type mice in vitro. Cytokines and chemokines across each mice were compared by cytokine array.
Results: Pyk2-KO mice didn’t show any apparent defective phenotype. While marked inflammation was observed in the aortic root of CAWS-treated WT mice, such vasculitis was barely detected in CAWS-treated Pyk2-KO mice. CAWS-induced NF-κB activation was also less observed in macrophages from Pyk2-KO mice. There were differences in some cytokines and chemokines production between mice.
Conclusion: We speculate that Pyk2 is involved in the pathogenesis of KD. Pyk2 might be a potential therapeutic target for KD.
Author Disclosures: C. Suzuki: None. A. Nakamura: None. M. Okigaki: None. N. Miura: None. N. Ohno: None. T. Yahata: None. A. Okamoto: None. A. Yoshioka: None. Y. Kuchitsu: None. K. Ikeda: None. K. Hamaoka: None.
- © 2015 by American Heart Association, Inc.