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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ito
Harumasa
H
Internal Medicine III, Iwate Medical University.
Sekimura
Kenshi
K
Sasaki
Nobuhito
N
Nitanai
Hiroo
H
Nakamura
Yutaka
Y
Shikanai
Toshiki
T
Mouri
Takashi
T
Yamauchi
Kohei
K
Inoue
Hiroshi
H
D001980:Bronchi / Q000737:chemistry / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000737:chemistry / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000502:physiology*; D006801:Humans; D019272:Leukocyte Elastase / Q000502:physiology*
D018840:HSP70 Heat-Shock Proteins; D019272:Leukocyte Elastase