The effects of progesterone on matrix metalloproteinases in cultured human gingival fibroblasts

Carol A. Lapp, Jennifer E. Lohse, Jill B. Lewis, Douglas P. Dickinson, Michael Billman, Philip Jerry Hanes, David F. Lapp

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Although pregnancy gingivitis is widely believed to result from elevated hormone concentrations, the mechanism(s) involved in the etiology of this condition remain unknown. Paradoxically, despite the apparent inflammation for a prolonged period, pregnancy gingivitis rarely progresses to periodontitis and usually resolves postpartum. We used several methods to test in vitro the hypothesis that the elevated progesterone levels of pregnancy might inhibit the production of some of the matrix metalloproteinases (MMPs) that are responsible for periodontal destruction. Methods: Cultured human gingival fibroblasts (GF) were tested in phenol red-free, serum-free medium with or without the progestogen, medroxyprogesterone acetate (MPA; 10-6 M), using interleukin-1β (IL-1β) to initiate immune responses and MMP production. These MMP responses were examined by macroarrays, reverse transcription-polymerase chain reaction (RT-PCR), zymograms, and enzyme-linked immunosorbent assay (ELISA). Results: Array analysis showed that pretreatment of GF with MPA reduced mRNA induction for MMPs-1, -3, and -10 in response to 6 to 8 hours incubation with IL-1β. RT-PCR confirmed, that after 24 hours with IL-β, GF pretreated with MPA had undetectable levels of mRNA for MMPs-1, -2, -3, -7, -10, and -13. Zymograms of culture media from this 24-hour period showed reduction in several proteolytic activities. Examination of such 24-hour media using ELISA for MMP-3 and pro-MMP-13 confirmed that secretion of these enzymes was upregulated by IL-1β and modulated downward by pretreatment with MPA. Conclusions: Production by GF of numerous MMPs in response to IL-1β was significantly reduced by progesterone. This steroidal modulation of proteolytic enzymes could help to explain why pregnancy gingivitis typically is not characterized by progression to periodontitis.

Original languageEnglish (US)
Pages (from-to)277-288
Number of pages12
JournalJournal of Periodontology
Volume74
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

Fingerprint

Matrix Metalloproteinases
Interleukin-1
Gingivitis
Progesterone
Fibroblasts
Matrix Metalloproteinase 1
Periodontitis
Pregnancy
Reverse Transcription
Enzyme-Linked Immunosorbent Assay
Prolonged Pregnancy
Matrix Metalloproteinase 13
Phenolsulfonphthalein
Matrix Metalloproteinase 3
Polymerase Chain Reaction
Messenger RNA
Medroxyprogesterone Acetate
Matrix Metalloproteinase 2
Serum-Free Culture Media
Progestins

Keywords

  • Fibroblasts, gingival
  • Gingivitis, pregnancy
  • Metalloproteinases, matrix
  • Pregnancy gingivitis
  • Progesterone/physiology

ASJC Scopus subject areas

  • Periodontics

Cite this

The effects of progesterone on matrix metalloproteinases in cultured human gingival fibroblasts. / Lapp, Carol A.; Lohse, Jennifer E.; Lewis, Jill B.; Dickinson, Douglas P.; Billman, Michael; Hanes, Philip Jerry; Lapp, David F.

In: Journal of Periodontology, Vol. 74, No. 3, 01.03.2003, p. 277-288.

Research output: Contribution to journalArticle

Lapp, Carol A. ; Lohse, Jennifer E. ; Lewis, Jill B. ; Dickinson, Douglas P. ; Billman, Michael ; Hanes, Philip Jerry ; Lapp, David F. / The effects of progesterone on matrix metalloproteinases in cultured human gingival fibroblasts. In: Journal of Periodontology. 2003 ; Vol. 74, No. 3. pp. 277-288.
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T1 - The effects of progesterone on matrix metalloproteinases in cultured human gingival fibroblasts

AU - Lapp, Carol A.

AU - Lohse, Jennifer E.

AU - Lewis, Jill B.

AU - Dickinson, Douglas P.

AU - Billman, Michael

AU - Hanes, Philip Jerry

AU - Lapp, David F.

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KW - Progesterone/physiology

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