title: Aeroallergen Der p 2 induces apoptosis of bronchial epithelial BEAS-2B cells via activation of both intrinsic and extrinsic pathway.
abstract: BACKGROUND
  Excessive apoptosis of airway epithelium is reported to induce airway remodeling and inhibited airway epithelium repair is highly associated with development of asthma and chronic obstructive pulmonary disease. Der p 2 is a major allergen derived from Dermatophagoides pteronyssinus and commonly causes airway hypersensitiveness and asthma; however, the connection between Der p 2 and epithelial apoptosis remains unclear. This study was aimed to explore whether Der p 2 induces apoptosis of airway epithelial cells and the underlying mechanisms.
  
  
  RESULTS
  Our results showed that recombinant Der p 2 (rDP2) inhibited cell growth and induced apoptosis of human bronchial epithelial cell BEAS-2B. Further investigation revealed that rDP2 increased intracellular reactive oxygen species, level of cytosolic cytochrome c and cleavage of caspase-9 and caspase-3. rDP2 also induced activation of p38 mitogen-activated protein kinase (P38) and c-Jun N-terminal kinase (JNK), and triggered proapoptotic signals including decrease of Bcl-2, increase of Bax and Bak, and upregulation of Fas and Fas ligand. In parallel, rDP2 inhibited glycogen synthase kinase 3beta and consequently enhanced degradation of cellular (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP). Involvement of toll-like receptor (TLR)2 in rDP2-induced apoptosis was also demonstrated using specific small inhibitory RNA.
  
  
  CONCLUSIONS
  Our findings indicate that rDP2 suppresses cell growth and trigger apoptosis of BEAS-2B cells, which may attribute to induction of both intrinsic and extrinsic pathway via TLR2 and P38/JNK signaling and c-FLIP degradation. It suggests that Der p 2 may aggravate respiratory disorders through enhancement of apoptosis and the consequent airway injury.
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, College of Medicine, Chung Shan Medical University, No.110, Sec. 1, Jianguo N. Road, Taichung, 402 Taiwan.
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, College of Medicine, Chung Shan Medical University, No.110, Sec. 1, Jianguo N. Road, Taichung, 402 Taiwan.
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Hong
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, College of Medicine, Chung Shan Medical University, No.110, Sec. 1, Jianguo N. Road, Taichung, 402 Taiwan ; Clinical Laboratory, Chung-Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Shao-Hsuan
authors.initials: SH
authors.lastname: Kao