Modulation by progesterone of interleukin-6 production by gingival fibroblasts.
The gingivitis associated with pregnancy has been attributed to increased concentrations of circulating estrogen and/or progesterone. However, the mechanism by which these steroids increase gingival inflammation is not known. Interleukin-6 (IL-6), a pleiotropic cytokine produced by many cell types including human gingival fibroblasts (hGF), is secreted in response to inflammatory challenges such as bacterial lipopolysaccharide and interleukin-1 (IL-1). This study tested the hypothesis that progesterone could modulate the local production of IL-6 by hGF. The effects of progesterone on IL-6 production were measured in vitro in serum-free, phenol red-free medium to eliminate possible effects of such medium additives. The concentration of IL-6 secreted into supernatant medium after a 24 hour challenge with IL-1 beta was estimated by radioimmunoassay. Total RNA from steroid-treated hGF was probed for IL-6 mRNA. In serum-free medium, progesterone dose-dependently and significantly (P < 0.05) inhibited IL-6 production by hGF, as did the glucocorticoids hydrocortisone (HC) and dexamethasone. At progesterone concentrations common in late pregnancy, IL-6 production was reduced to levels 40 to 50% of control. In addition, mRNA was significantly down-regulated by progesterone and HC, at both basal levels and after IL-1 beta challenge. These results suggest that high levels of progesterone during pregnancy affect the development of localized inflammation by down-regulation of IL-6 production, rendering the gingiva less efficient at resisting the inflammatory challenges produced by bacteria.
Lapp
C A
CA
Department of Oral Biology, Medical College of Georgia, Augusta, USA.
Thomas
M E
ME
Lewis
J B
JB
D000704:Analysis of Variance; D016895:Culture Media, Serum-Free; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000276:immunology / Q000378:metabolism*; D005891:Gingivitis / Q000209:etiology / Q000276:immunology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000276:immunology; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D018709:Statistics, Nonparametric; D000093242:Interleukin-6 Inhibitors
D016895:Culture Media, Serum-Free; D003907:Dexamethasone; D006854:Hydrocortisone; D015850:Interleukin-6; D011374:Progesterone; D012333:RNA, Messenger; D000093242:Interleukin-6 Inhibitors