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 t ransforming 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 cont rast, incubation of these cultures with 100 nM of prostaglandin E(2) ( PGE(2)) reduced enzyme activity levels by 40 to 50% although steady-st ate mRNA was not changed. Consistent with the effect of PGE(2), the pr esence of indomethacin stimulated levels of secreted enzyme activity. When present in cultures simultaneously with TGF-beta(1), PGE(2) preve nted the stimulation beyond control levels seen with TGF-beta(1) alone . Densitometry of protein bands immunoprecipitated by antibody to lysy l oxidase indicated that the degree of conversion of the 50 kD proenzy me 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 p rotein was increased by TGF-beta(1) and decreased by PGE(2), These res ults indicate that TGE-beta(1) and specific prostaglandin(s) exert opp osing effects on the expression of lysyl oxidase in these lung fibrobl asts.