Differences in MAP kinase phosphorylation in response to mechanical strain in asthmatic fibroblasts.
BACKGROUND
Mechanical strain alters protein expression. It results in phosphorylation of MAP kinases and up-regulation of extracellular matrix proteins. We investigated whether phosphorylation of MAP kinase family members was increased in response to mechanical strain in fibroblasts from asthmatic patients (AF) and normal controls (NF), and whether phosphorylation of these signaling molecules would be different in the two cell populations.


METHODS
Fibroblasts were obtained from mild, atopic asthmatics and non-atopic volunteers using endobronchial biopsy. Cells were grown on flexible, collagen I-coated membranes, and subjected to mechanical strain (Flexercell). MAP kinase phosphorylation was measured at baseline, and during one hour of strain. We also examined the effect of strain on proteoglycan production.


RESULTS
At baseline, there was increased phosphorylation of ERK1/2 and p38, and decreased phosphorylation of JNK in AF vs NF. During strain in NF, p38 phosphorylation was increased. Conversely in AF, strain resulted in an increase in JNK phosphorylation, had no effect on phosphorylation of p38, and resulted in a decrease in ERK1/2 phosphorylation. There was a significant increase in versican protein production after 24 h strain in both AF and NF. JNK inhibition reversed the strain-induced increase in versican in NF, but had no effect in AF.


CONCLUSIONS
These results show that there are phenotypic differences in MAP kinase phosphorylation in AF vs NF, and that different signaling pathways are involved in transducing mechanical stimuli in these two populations of cells.
Le Bellego
Frédérique
F
Meakins-Christie Laboratories, McGill University Hospital Center, Montreal, Quebec, Canada. frederique.lebellego@mcgill.ca
Plante
Sophie
S
Chakir
Jamila
J
Hamid
Qutayba
Q
Ludwig
Mara S
MS
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000201:enzymology*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D013314:Stress, Mechanical
D048049:Extracellular Signal-Regulated MAP Kinases