PMID- 7734515
OWN - NLM
STAT- MEDLINE
DCOM- 19950608
LR  - 20071114
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 6
IP  - 2
DP  - 1995 Feb
TI  - Replication-deficient adenovirus induces expression of interleukin-8 by airway 
      epithelial cells in vitro.
PG  - 145-53
AB  - Preclinical studies with first-generation adenovirus (Ad) vectors administered in 
      vivo to the respiratory tract have demonstrated a nonspecific host response 
      consisting, in part, of parenchymal neutrophil accumulation followed by 
      mononuclear cell and macrophage accumulation. We hypothesized that the mechanism 
      for this host response might be the elaboration of interleukin-8 (IL-8) and 
      monocyte chemoattractant protein-1 (MCP-1) from the airway epithelium following 
      the exposure to Ad. To evaluate this hypothesis, we infected A549 cells (a 
      human-derived lung epithelial cell line) in vitro with an adenovirus type 5 
      (Ad5)-based vector expressing a nuclear targeted beta-galactosidase enzyme 
      (Av1LacZ4). We found that cellular transduction was efficient, resulting in gene 
      delivery to 85.5% +/- 3.9% of the cell monolayer after 96 hr. Importantly, IL-8 
      mRNA transcript levels in Av1LacZ4-transduced cells were significantly higher 
      than uninfected controls by 24 hr and remained elevated for 96 hr. IL-8 protein 
      secretion from Av1LacZ4-transduced cells was increased for the same period. The 
      Av1LacZ4-transduced A549 cells also showed a neutrophil chemoattractant activity 
      higher than control cells, measurable at 24 hr, and persisting for 96 hr. The 
      chemoattractant activity could be neutralized by a specific monoclonal antibody 
      to IL-8. Whereas Av1LacZ4 transduction induced IL-8 gene expression, there was a 
      lack of expression of MCP-1 by A549 cells. These observations demonstrate that 
      the gene delivery to the airway epithelium using the Ad5-based expression vector 
      results in IL-8 gene activation in these cells, which may contribute to the 
      described inflammatory host response.
FAU - Amin, R
AU  - Amin R
AD  - Division of Pulmonary Medicine, Children's Hospital Medical Center, Cincinnati, 
      OH 45229-3039, USA.
FAU - Wilmott, R
AU  - Wilmott R
FAU - Schwarz, Y
AU  - Schwarz Y
FAU - Trapnell, B
AU  - Trapnell B
FAU - Stark, J
AU  - Stark J
LA  - eng
GR  - 51832/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-8)
RN  - 0 (RNA, Messenger)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Adenoviruses, Human/*genetics
MH  - Antibodies, Monoclonal
MH  - Cell Line
MH  - Chemokine CCL2
MH  - Chemotactic Factors/biosynthesis
MH  - Chemotaxis
MH  - Cytokines/biosynthesis
MH  - Epithelial Cells
MH  - Gene Expression
MH  - Gene Transfer Techniques
MH  - Genes, Reporter/genetics
MH  - Genetic Vectors/*genetics
MH  - Humans
MH  - Interleukin-8/*biosynthesis/immunology
MH  - Lung/cytology/*immunology/metabolism
MH  - Neutralization Tests
MH  - Neutrophils/cytology
MH  - RNA, Messenger/biosynthesis
MH  - beta-Galactosidase/biosynthesis/genetics
EDAT- 1995/02/01 00:00
MHDA- 1995/02/01 00:01
CRDT- 1995/02/01 00:00
PHST- 1995/02/01 00:00 [pubmed]
PHST- 1995/02/01 00:01 [medline]
PHST- 1995/02/01 00:00 [entrez]
AID - 10.1089/hum.1995.6.2-145 [doi]
PST - ppublish
SO  - Hum Gene Ther. 1995 Feb;6(2):145-53. doi: 10.1089/hum.1995.6.2-145.