REGULATION OF LYSYL OXIDASE EXPRESSION IN LUNG FIBROBLASTS BY TRANSFORMING GROWTH FACTOR-BETA(1) AND PROSTAGLANDIN E(2)

The regulation of lysyl oxidase produced by cultured, lipid-enriched, neonatal rat lung fibroblasts was explored. The presence of 40 pM of transforming growth factor-beta(1) (TGF-beta(1)) in overnight cultures increased levels of enzyme secreted into the medium by 1.6-fold while steady-state levels of lysyl oxidase mRNA increased similarly. In contrast, incubation of these cultures with 100 nM of prostaglandin E(2) (PGE(2)) reduced enzyme activity levels by 40 to 50% although steady-state mRNA was not changed. Consistent with the effect of PGE(2), the presence of indomethacin stimulated levels of secreted enzyme activity. When present in cultures simultaneously with TGF-beta(1), PGE(2) prevented the stimulation beyond control levels seen with TGF-beta(1) alone. Densitometry of protein bands immunoprecipitated by antibody to lysyl oxidase indicated that the degree of conversion of the 50 kD proenzyme to the 29 kD enzyme was not significantly altered by TGF-beta(1) or PGE(2). However, the net accumulation of all forms of lysyl oxidase protein was increased by TGF-beta(1) and decreased by PGE(2), These results indicate that TGE-beta(1) and specific prostaglandin(s) exert opposing effects on the expression of lysyl oxidase in these lung fibroblasts.