Mucin secretion in the rat tracheal epithelial cells by epidermal growth factor and Pseudomonas aeruginosa extracts.
BACKGROUND
Hypersecretion of mucin due to goblet cell hyperplasia is frequently encountered in many chronic airway diseases, such as chronic bronchitis, bronchiectasis, bronchial asthma and cystic fibrosis. Even in normal individuals, viral infection or bacterial pneumonia frequently provoke huge amounts of bronchial secretions which may cause airway obstruction. The production of mucin was regulated by epidermal growth factor (EGF) in vitro. To know whether this EGF system regulates mucin secretion in vivo and Pseudomonas also stimulates the mucin secretion by the same pathway, we studied these relationships in the cultured rat tracheal epithelial cells.


METHODS
Rat tracheal epithelial cells were obtained by pronase dissociation from the male Fisher 344 rats. When cells became confluent, they were divided into 6 groups and stimulated with either EGF for 24 hours or Pseudomonas extracts for 12 hours with or without selective EGF-R tyrosine kinase inhibitor tyrphostin AG1478.


RESULTS
We found that both EGF and Pseudomonas extracts phosphorylated the tyrosine residue in the EGF receptor from the rat tracheal epithelial cells and this tyrosine phosphorylation was nearly completely blocked by selective EGF-R tyrosine kinase inhibitor tyrphostin AG1478. The mucin secretion was also stimulated by either EGF or Pseudomonas extracts but more strong secretion of mucin and MUC5AC gene expression in the rat tracheal epithelial cell was done by Pseudomonas extracts.


CONCLUSIONS
These data suggest that Pseudomonas secretes the mucin by way of the EGF receptor and MUC5AC gene expression and the inhibitors of EGF receptor tyrosine phosphorylation would be useful to prevent the huge production of mucin due to Pseudomonas aeruginosa lung infection.
Song
J S
JS
Department of Internal Medicine, St. Mary's Hospital, Catholic University Medical College, #62, Yeoi-Do Dong, Young-Dung Po Gu, Seoul, Korea, 150-713.
Hyun
S W
SW
Lillihoj
E
E
Kim
B T
BT
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D008297:Male; D023421:Models, Animal; D055271:Mucin 5AC; D009077:Mucins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D011550:Pseudomonas aeruginosa; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*
C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor