Effect of phenytoin on the production of interleukin-6 and interleukin-8 in human gingival fibroblasts.
The in vitro effect of phenytoin (PHT) on the production of interleukin-6 (IL-6) and interleukin-8 (IL-8) in human gingival fibroblasts, challenged with or without interleukin-1beta (IL-1beta), was studied. PHT (20 microg/ml) alone increased the mRNA level for both IL-6 and IL-8, as well as synergistically enhancing the production of IL-6 and IL-8, at both transcriptional and translational level in fibroblasts challenged with IL-1beta (30 pg/ml). The stimulatory effect of PHT on IL-1beta-induced IL-6 production was strongly reduced by the specific cyclooxygenase-2 inhibitor NS-398 (1 microM). The anti-inflammatory drug, dexamethasone (1 microM), abolished the production of both IL-6 and IL-8 in gingival fibroblasts challenged with PHT in the presence or absence of IL-1beta. The ability of PHT, alone as well as in combination with IL-1, to upregulate the production of IL-6 and IL-8 in human gingival fibroblasts may contribute to enhanced recruitment and activation of inflammatory cells. This effect of PHT may thereby give a prerequisite for the establishment of an interaction between cytokines and connective tissue cells in the periodontal tissue, which is suggested to lead to gingival overgrowth.
Modéer
T
T
Department of Pediatric Dentistry, Karolinska Institutet, Huddinge, Sweden.
Domeij
H
H
Andurén
I
I
Mustafa
M
M
Brunius
G
G
D000293:Adolescent; D000927:Anticonvulsants / Q000494:pharmacology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D010672:Phenytoin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D013268:Stimulation, Chemical; D015854:Up-Regulation
D000927:Anticonvulsants; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D012333:RNA, Messenger; D010672:Phenytoin