Cytoprotective effects of heat shock protein-70 in bronchial epithelium against neutrophil elastase-induced cell injury

• Published in: Arerugi Vol. 55; no. 7; p. 820
• Main Authors: Ito, Harumasa, Sekimura, Kenshi, Sasaki, Nobuhito, Nitanai, Hiroo, Nakamura, Yutaka, Shikanai, Toshiki, Mouri, Takashi, Yamauchi, Kohei, Inoue, Hiroshi
• Format: Journal Article
• Language: Japanese
• Published: Japan 01.07.2006
• Subjects: Bronchi - chemistry; Bronchi - physiology; Cells, Cultured; Epithelial Cells - chemistry; Epithelial Cells - physiology; HSP70 Heat-Shock Proteins - analysis; HSP70 Heat-Shock Proteins - physiology; Humans; Leukocyte Elastase - physiology
• ISSN: 0021-4884; 1347-7935
• DOI: 10.15036/arerugi.55.820

Neutrophil releases several mediators during inflammation, including neutrophil elastase (NE) that impairs bronchial epithelial function. The stress response and stress proteins protect cells against a variety of cytotoxic conditions. Accordingly, we tested the hypothesis that bronchial epithelial heat shock protein (Hsp-70) would protect a NE-induced cell injury. Bronchial epithelial cells (BECs) obtained by bronchial brushing under bronchoscopy were cultured and used for experiments. Expression of Hsp-70 in BECs was confirmed by Western blot and flowcytometric analysis. To test Hsp-70 in BECs, induction of Hsp-70 protein into BECs was carried out by liposome-based delivery system. Introduction of Hsp-70 into BECs were examined by direct fluorescence microscope examination and flowcytometric analysis. NE-induced cytotoxicity was evaluated by cell culture supernatant LDH assay and cell detachment assay. Higher expressions of Hsp-70 were observed in BECs, which were induced by sodium arsenite. Over expression of Hsp-70 in BECs reduced NE-induced cell injury. Introduction of Hsp-70 protein into BECs by liposomal delivery decreased LDH release, and inhibited necrosis and apoptosis of the cells by NE as compared to untreated control. These data suggested that Hsp-70 in BECs may inhibit NE-induced airway epithelial damage. Liposomal delivery of Hsp-70 into BECs may be a possible means of protecting bronchial epithelium against inflammatory airway diseases including acute and chronic bronchitis.