Inhibition of fibroblast-like cell proliferation by interleukin-1 blockers, CK-119 and CK-122.
OBJECTIVE
To study potent and nontoxic agents to inhibit fibroblast proliferation.


METHODS
Fibroblast-like corneal and conjunctival cells were cultured and inhibited by interleukin-1 (IL-1) blockers, dihydropyridazino-pyridazines CK-119 and CK-122. The cell growth and syntheses of DNA, RNA, and protein after IL-1 blocker incubation were determined.


RESULTS
CK-119 and CK-122 inhibited cell growth of corneal fibroblast at 30 mg.L-1. DNA and RNA syntheses in corneal fibroblasts were markedly inhibited by CK-119 and CK-122 whereas protein synthesis was either unaffected or mostly enhanced at 30-100 mg.L-1 and 100-300 mg.L-1, respectively. Similar results were obtained in conjunctival cell cultures by CK-119 and CK-122 at 3-10 mg.L-1 and 30-100 mg.L-1, respectively.


CONCLUSIONS
CK-119 and CK-122 are potent IL-1 blockers to inhibit cell growth of fibroblast-like corneal and conjunctival cells mainly through the inhibition of DNA and RNA syntheses but not protein synthesis.
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Institute of Ocular Pharmacology, TX A&M University College of Medicine, College Station 77843-1114, USA.
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003228:Conjunctiva / Q000166:cytology*; D003315:Cornea / Q000166:cytology*; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D007529:Isoflavones; D011724:Pyridazines / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D011817:Rabbits
C120268:CK 119; C120269:CK 122; D007375:Interleukin-1; D007529:Isoflavones; D011724:Pyridazines; D012313:RNA; D004247:DNA