PMID- 17319946
OWN - NLM
STAT- MEDLINE
DCOM- 20070418
LR  - 20181201
IS  - 1471-2199 (Electronic)
IS  - 1471-2199 (Linking)
VI  - 8
DP  - 2007 Feb 23
TI  - Interleukin-4 inhibition of interleukin-1-induced expression of matrix 
      metalloproteinase-3 (MMP-3) is independent of lipoxygenase and PPARgamma 
      activation in human gingival fibroblasts.
PG  - 12
AB  - BACKGROUND: Interleukin 4 (IL-4) has been shown to suppress interleukin-1 (IL-1) 
      induced expression of matrix metalloproteinase-3 (MMP-3) in human synovial and 
      gingival fibroblasts, but the mechanism of suppression has not been determined. 
      Activators of peroxisome proliferator-activated receptor-gamma (PPARgamma) have 
      been shown to inhibit cytokine induced expression of MMPs in other cell types, 
      and IL-4 has been shown to activate PPARgamma by stimulating production of 
      ligands through the lipoxygenase pathway. It has been suggested that PPARgamma 
      may inhibit expression of MMPs by competing with transcription factor AP-1 for 
      binding to a putative composite binding element in the promoters. The objective 
      of this study was to determine whether the suppressive effects of IL-4 on the 
      IL-1 induced expression of MMP-3 involve activation of lipoxygenase and/or 
      PPARgamma. RESULTS: Western blotting revealed the presence of PPARgamma in 
      nuclear extract of HGF. IL-1 induced binding of nuclear extract to the putative 
      composite PPRE/AP-1 site was diminished in the presence of pioglitazone, but 
      there was no evidence of any change in the composition of the retarded complexes, 
      and no evidence of PPARgamma binding to this site. Nordihydroguaiaretic acid 
      (NDGA), a non-selective lipoxygenase inhibitor, and MK886, a specific inhibitor 
      of 5-lipoxygenase, induced MMP-3 expression synergistically with IL-1. However 
      IL-4 was still able to inhibit MMP-3 expression in the presence of NDGA or MK886 
      and IL-1. Activation of PPARgamma with pioglitazone not only failed to inhibit 
      IL-1 induced expression of MMP-3 mRNA, but rather super-induced MMP-3 in the 
      presence of IL-1. PPARgamma antagonist GW9662 failed to abolish the suppressive 
      effects of IL-4. Another PPARgamma activator, 15-deoxy-Delta12,14prostaglandin J2 
      (15dPGJ2), also super-induced MMP-3 mRNA, and this was due at least in part to 
      increased transcription. CONCLUSION: IL-4 suppression of IL-1-induced MMP-3 
      expression in HGF is independent of lipoxygenase activity and activation of 
      PPARgamma. Super-induction of MMP-3 by pioglitazone may have important 
      implications for patients using pioglitazone to treat type II diabetes in the 
      presence of chronic inflammation.
FAU - Stewart, Denise
AU  - Stewart D
AD  - Department of Biochemistry and Molecular Biology, Philadelphia College of 
      Osteopathic Medicine, Philadelphia, PA, USA. denisest@pcom.edu 
      <denisest@pcom.edu>
FAU - Javadi, Masoud
AU  - Javadi M
FAU - Chambers, Mariah
AU  - Chambers M
FAU - Gunsolly, Chad
AU  - Gunsolly C
FAU - Gorski, Grzegorz
AU  - Gorski G
FAU - Borghaei, Ruth C
AU  - Borghaei RC
LA  - eng
GR  - R15 DE016277/DE/NIDCR NIH HHS/United States
GR  - R15 DE016277-02/DE/NIDCR NIH HHS/United States
GR  - R15DE16277/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070223
PL  - England
TA  - BMC Mol Biol
JT  - BMC molecular biology
JID - 100966983
RN  - 0 (Interleukin-1)
RN  - 0 (PPAR gamma)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transcription Factor AP-1)
RN  - 207137-56-2 (Interleukin-4)
RN  - EC 1.13.11.12 (Lipoxygenase)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Binding Sites
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Enzyme Activation
MH  - Fibroblasts/enzymology/metabolism
MH  - Gingiva/cytology/enzymology/*metabolism
MH  - Humans
MH  - Interleukin-1/*metabolism
MH  - Interleukin-4/*pharmacology
MH  - Lipoxygenase/*metabolism
MH  - Matrix Metalloproteinase 3/genetics/*metabolism
MH  - PPAR gamma/*metabolism
MH  - Pioglitazone
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Thiazolidinediones/pharmacology
MH  - Transcription Factor AP-1/genetics
MH  - Transfection
PMC - PMC1810308
EDAT- 2007/02/27 09:00
MHDA- 2007/04/19 09:00
PMCR- 2007/02/23
CRDT- 2007/02/27 09:00
PHST- 2006/07/26 00:00 [received]
PHST- 2007/02/23 00:00 [accepted]
PHST- 2007/02/27 09:00 [pubmed]
PHST- 2007/04/19 09:00 [medline]
PHST- 2007/02/27 09:00 [entrez]
PHST- 2007/02/23 00:00 [pmc-release]
AID - 1471-2199-8-12 [pii]
AID - 10.1186/1471-2199-8-12 [doi]
PST - epublish
SO  - BMC Mol Biol. 2007 Feb 23;8:12. doi: 10.1186/1471-2199-8-12.