Induction of c-fos by prostaglandin F2 alpha in human ciliary smooth muscle cells.
OBJECTIVE
To evaluate the induction of the proto-oncogene c-fos in cultured human ciliary muscle cells by prostaglandin F2 alpha (PGF2 alpha) by 17-phenyltrinor-PGF 2 alpha.


METHODS
Human ciliary muscle cells were grown to confluency in monolayer cell culture, placed in medium containing 1% fetal bovine serum for 5 days, treated by addition of PGF2 alpha or the trinor derivative, fixed, and then immunocytochemically stained using an antibody to c-Fos, the protein product of the translation of c-fos.


RESULTS
After treatment with either agonist, the mean induction score (proportion of brightly immunostained nuclei) increased to a maximal level during the first hour and returned to basal levels 4 to 8 hours after treatment. Increasing the agonist concentration increased the maximal level, but had no effect on the time course of the response. The dose responses after 1 hour of treatment with PGF2 alpha or 17-phenyltrinor-PGF2 alpha increased similarly between 1.6 x 10(-9) M and 2 x 10(-7) M. When treated with 1 x 10(-6) M of either agonist, however, the induction was half that obtained at 2 x 10(-7) M.


CONCLUSIONS
Exposure of ciliary smooth muscle cells to either PGF2 alpha or 17-phenyltrinor-PGF2 alpha induces an immediate early gene expression response that is similar to c-Fos induction in other cell systems. These results establish the basis for future investigations evaluating the potential role of c-fos induction in mediating the effects of PGF2 alpha on uveoscleral outflow.
Lindsey
J D
JD
Glaucoma Center, University of California at San Diego, La Jolla 92093.
To
H D
HD
Weinreb
R N
RN
D002478:Cells, Cultured; D002924:Ciliary Body / Q000166:cytology / Q000187:drug effects*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; C013646:17-phenyl-18,19,20-trinorprostaglandin F2 alpha; D015237:Dinoprost