Abstract
Asthma is a common chronic inflammatory disease characterized by reversible airflow obstruction and airway hyperresponsiveness. Bronchial epithelial cells are the frontline protective barrier against mumerous factors of infectious diseases. The cells also play an essential role in antimicrobial function and release several cytokines and chemokines to modulate lung inflammation. Eosinophil cationic protein (ECP), secreted by activated eosinophils, serves as a biomarker for asthma. Recently, a novel cell penetrating peptide derived from a unique heparin binding motif of ECP (CPPecp) has been identified. Biodistribution of CPPecp in vivo mainly accumulated in bronchus and lung epithelial tissues by intranasal and intravenous injection. In addition, asthmatic animal model using BALB/C mice sensitized and challenged by house dust mite (HDM) was established, and physiological functions including pause enhancement (Penh), differenial cell counts in the absence and presence of CPPecp were analyzed. Administration of CPPecp in asthmatic mice showed significant reduction in airway hyperreactivity and asthma-related chemokine expression, suggesting that CPPecp reduced HDM-induced airway inflammation in vivo. Furthermore, regulatory effects of ECP and CPPecp in bronchial epithelial cells were investigated by real-time PCR and enzyme-linked immunosorbent assay (ELISA). ECP up-regulated gene and protein expression of several chemokines, whereas CPPecp down-regulated the expression levels of specific chemokines induced by ECP and interleukin-4 (IL-4), indicating that CPPecp played an important role in regulating inflammatory response of bronchial epithelial cells. Regulatory roles of CPPecp in specific chemokine pathway was further investigated. Western blotting assay indicated that CPPecp decreased ECP- and IL-4-induced transcription factor activiation. This study demonstrated that ECP up-regulated expression of specific chemokine by activating transcription factor whereas CPPecp attenuated development of allergic airway inflammation and airway hyperresponsiveness both in vitro and in vivo. Hence CPPecp might have a potential to be developed as a novel non-steroidal asthma treatment drug.