PMID- 22934840
OWN - NLM
STAT- MEDLINE
DCOM- 20131111
LR  - 20181202
IS  - 1943-3670 (Electronic)
IS  - 0022-3492 (Linking)
VI  - 84
IP  - 5
DP  - 2013 May
TI  - Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, and 
      inflammation in cyclosporine A-induced gingival enlargement: a pilot in vitro 
      study using a three-dimensional model of the human oral mucosa.
PG  - 634-40
LID - 10.1902/jop.2012.120224 [doi]
AB  - BACKGROUND: It has been suggested that cyclosporine A (CsA) induces gingival 
      enlargement by promoting an increase in the gingival extracellular matrix (ECM). 
      Nonetheless, the variable occurrence of CsA-induced gingival enlargement in 
      patients receiving this medication indicates a multifactorial pathogenesis. 
      Clinical observations suggest that local inflammation is associated with the 
      development and severity of CsA-induced gingival enlargement. Therefore, the 
      purpose of this study is to investigate the effects of CsA and inflammation on 
      the production of ECM homeostatic mediators. METHODS: The effects of CsA and 
      inflammation (as assessed using interleukin [IL]-1beta) on the secretion of 
      mediators involved in ECM homeostasis were determined using fibroblast monolayers 
      and three-dimensional (3D) models of the human oral mucosa. Fibroblast monolayers 
      and 3D cultures were treated with CsA alone or in combination with IL-1beta for up 
      to 72 hours, and the secretion of matrix metalloproteinases (MMPs) 1, 2, 3, 8, 9, 
      10, and 13 and tissue inhibitors of MMPs (TIMPs) 1, 2, and 4 into the culture 
      medium was assessed using enzyme-linked immunoassay-based antibody arrays. 
      RESULTS: Fibroblast monolayers responded to CsA with no changes in the secretion 
      of ECM mediators. Conversely, 3D cultures responded to CsA treatment with a 
      reduction in MMP-10 secretion. IL-1beta alone triggered higher secretory levels of 
      MMPs in both fibroblast monolayers (MMP-3 and MMP-10) and 3D cultures (MMP-9 and 
      MMP-10). Importantly, fibroblast monolayers and 3D cultures treated with a 
      combination of IL-1beta and CsA showed a decrease in the MMP-1/TIMP-1 ratio. 
      CONCLUSIONS: These data support the hypothesis that inflammation may alter the 
      pathogenesis of CsA-induced gingival enlargement by promoting a synergistic 
      decrease in the MMP-1/TIMP-1 ratio.
FAU - Johanson, Matthew
AU  - Johanson M
AD  - Department of Periodontics, The University of Texas Health Science Center, San 
      Antonio, TX, USA.
FAU - Zhao, Xiang R
AU  - Zhao XR
FAU - Huynh-Ba, Guy
AU  - Huynh-Ba G
FAU - Villar, Cristina C
AU  - Villar CC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120830
PL  - United States
TA  - J Periodontol
JT  - Journal of periodontology
JID - 8000345
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Analysis of Variance
MH  - Cells, Cultured
MH  - Cyclosporine/adverse effects
MH  - Extracellular Matrix Proteins/metabolism
MH  - Gingiva/cytology/metabolism
MH  - Gingival Overgrowth/*chemically induced/*enzymology/etiology
MH  - Humans
MH  - Inflammation/*complications/metabolism
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Matrix Metalloproteinase 1/*metabolism
MH  - Matrix Metalloproteinases/*metabolism
MH  - Models, Anatomic
MH  - Mouth Mucosa/cytology/*enzymology
MH  - Pilot Projects
MH  - Statistics, Nonparametric
MH  - Tissue Inhibitor of Metalloproteinase-1/*metabolism
MH  - Tissue Inhibitor of Metalloproteinases/*metabolism
EDAT- 2012/09/01 06:00
MHDA- 2013/11/12 06:00
CRDT- 2012/09/01 06:00
PHST- 2012/09/01 06:00 [entrez]
PHST- 2012/09/01 06:00 [pubmed]
PHST- 2013/11/12 06:00 [medline]
AID - 10.1902/jop.2012.120224 [doi]
PST - ppublish
SO  - J Periodontol. 2013 May;84(5):634-40. doi: 10.1902/jop.2012.120224. Epub 2012 Aug 
      30.