| The effects of progesterone on matrix metalloproteinases in cultured human gingival fibroblasts. | |
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MedLine Citation:
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PMID: 12710746 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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-1beta (IL-1beta) 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-1beta. RT-PCR confirmed, that after 24 hours with IL-1beta , 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-1beta and modulated downward by pretreatment with MPA. CONCLUSIONS: Production by GF of numerous MMPs in response to IL-1beta 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. |
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Authors:
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Carol A Lapp; Jennifer E Lohse; Jill B Lewis; Douglas P Dickinson; Michael Billman; Philip J Hanes; David F Lapp |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of periodontology Volume: 74 ISSN: 0022-3492 ISO Abbreviation: J. Periodontol. Publication Date: 2003 Mar |
Date Detail:
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Created Date: 2003-04-24 Completed Date: 2003-07-10 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8000345 Medline TA: J Periodontol Country: United States |
Other Details:
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Languages: eng Pagination: 277-88 Citation Subset: D; IM |
Affiliation:
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Department of Oral Biology, Medical College of Georgia, Augusta, GA 30912, USA. clapp@mail.mcg.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Cells, Cultured Collagenases / antagonists & inhibitors Enzyme Inhibitors / pharmacology Female Fibroblasts / cytology, enzymology* Gingiva / cytology, enzymology* Glycoproteins / antagonists & inhibitors Humans Interleukin-1 / pharmacology Male Matrix Metalloproteinase 1 / antagonists & inhibitors Matrix Metalloproteinase 10 Matrix Metalloproteinase 13 Matrix Metalloproteinase 2 / antagonists & inhibitors Matrix Metalloproteinase 3 / antagonists & inhibitors Matrix Metalloproteinase 7 / antagonists & inhibitors Matrix Metalloproteinases / antagonists & inhibitors*, genetics Medroxyprogesterone Acetate / pharmacology* Metalloendopeptidases / antagonists & inhibitors Pregnancy Progesterone Congeners / pharmacology* RNA, Messenger / antagonists & inhibitors Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Glycoproteins; 0/Interleukin-1; 0/Progesterone Congeners; 0/RNA, Messenger; 71-58-9/Medroxyprogesterone Acetate; EC 3.4.24.-/Collagenases; EC 3.4.24.-/MMP13 protein, human; EC 3.4.24.-/Matrix Metalloproteinase 13; EC 3.4.24.-/Matrix Metalloproteinases; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.17/Matrix Metalloproteinase 3; EC 3.4.24.22/Matrix Metalloproteinase 10; EC 3.4.24.23/Matrix Metalloproteinase 7; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.7/Matrix Metalloproteinase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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