Interleukin-1 beta and phenytoin reduce alpha 1 (I) procollagen mRNA expression in human gingival fibroblasts.
Effects of and interactions between interleukin-1 beta (IL-1 beta) and phenytoin (PHT) on alpha 1 (I) procollagen gene and protein expression in human gingival fibroblasts and its relation to prostaglandin E2 (PGE2) formation were studied. IL-1 beta (300 pg/ ml) reduced the steady-state level of alpha 1 (I) procollagen mRNA by 50% and decreased the amount of procollagen I by 35%. PHT (10 micrograms/ml) reduced the level of alpha 1 (I) procollagen mRNA by 40% but the amount of procollagen I in the medium was unchanged. In combination with IL-1 beta, PHT potentiated the inhibitory effect of IL-1 beta on alpha 1 (I) procollagen mRNA level that was accompanied by an increased PGE2 formation. Preincubation with indomethacin (10(-6) M) partially reduced the inhibitory effect of IL-1 beta as well as of IL-1 beta in combination with PHT on the mRNA level of alpha 1 (I) procollagen. The inhibitory effect of PHT was unaffected by indomethacin treatment. Addition of exogenous PGE2 (> or = 10 nM) dose-dependently reduced steady-state level of alpha 1 (I) procollagen mRNA as well as the amount of procollagen 1. The study indicates that IL-1 reduces the expression of alpha 1 (I) procollagen mRNA in human gingival fibroblasts partly by a prostaglandin endoperoxide (PGH) synthase-mediated pathway and partly by a PGH-synthase independent pathway, whereas PHT reduces alpha 1 (I) procollagen gene expression by a PGH-synthase independent pathway. The potentiation of the inhibitory effect of IL-1 induced by PHT was mediated mainly by a PGH-synthase dependent pathway.
Modéer
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Department of Pediatric Dentistry, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden.
Andurén
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Bengtsson
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A
Andersson
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G
D000927:Anticonvulsants / Q000494:pharmacology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D002648:Child; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D010672:Phenytoin / Q000494:pharmacology*; D011347:Procollagen / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics
D000927:Anticonvulsants; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D011347:Procollagen; D012333:RNA, Messenger; D010672:Phenytoin; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin