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The Effects of Progesterone on Matrix Metalloproteinases in Cultured Human Gingival Fibroblasts
Author(s) -
Lapp Carol A.,
Lohse Jennifer E.,
Lewis Jill B.,
Dickinson Douglas P.,
Billman Michael,
Hanes Philip J.,
Lapp David F.
Publication year - 2003
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2003.74.3.277
Subject(s) - matrix metalloproteinase , andrology , gingivitis , interleukin , medroxyprogesterone acetate , endocrinology , medicine , biology , chemistry , estrogen , cytokine , dentistry
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‐1β, 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. J Periodontol 2003;74:277‐288.