Adenoviral E1A suppresses secretory leukoprotease inhibitor and elafin secretion in human alveolar epithelial cells and bronchial epithelial cells.
BACKGROUND
An imbalance between neutrophil protease and surrounding antiprotease levels has been shown to be important in the pathogenesis of chronic obstructive pulmonary disease (COPD). Adenoviral E1A DNA and protein are frequently detected in the lungs of COPD patients. As secretory leukoprotease inhibitor (SLPI) and elafin/skin-derived antileukoproteinase (SKALP) are locally produced in the lung and inhibit neutrophil elastase activity, we hypothesized that adenoviral E1A might affect the production of these antiproteases.


OBJECTIVE
To examine the effect of E1A on SLPI and elafin/SKALP secretion in A549 (alveolar epithelial) cells and primary human bronchial epithelial (HBE) cells.


METHODS
SLPI and elafin/SKALP were quantitated from cell culture supernatants using an ELISA. SLPI mRNA expression was examined by Northern blotting, and SLPI promoter activity was measured using a reporter gene assay.


RESULTS
E1A significantly suppressed SLPI and elafin/SKALP secretion by A549 cells upon interleukin (IL)-1beta stimulation. E1A also suppressed SLPI and elafin/SKALP secretion by HBE cells. SLPI mRNA expression in A549 cells was suppressed by E1A regardless of IL-1beta stimulation. IL-1beta-induced SLPI promoter activity was suppressed by E1A gene transfection into A549 cells.


CONCLUSIONS
Our findings of adenoviral E1A-mediated suppression of SLPI and elafin/SKALP secretion suggest that E1A may be involved in the enhancement of alveolar damage and play a role in the COPD process.
Higashimoto
Yuji
Y
Department of Internal Medicine, Wakayama Medical University Kihoku Hospital, 219 Myoji, Katsuragi-cho, Ito-gun, Wakayama Prefecture 649-7113, Japan. yhigashi@wakayama-med.ac.jp
Yamagata
Yuko
Y
Iwata
Takuya
T
Ishiguchi
Tadashi
T
Okada
Morihiro
M
Masuda
Mitsunori
M
Satoh
Hiroaki
H
Itoh
Hidekazu
H
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000494:pharmacology / Q000502:physiology*; D000258:Adenovirus Infections, Human / Q000821:virology; D001980:Bronchi / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000821:virology*; D053481:Secretory Leukocyte Peptidase Inhibitor; D017735:Virus Latency
D017500:Adenovirus E1A Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor