PMID- 17289798
OWN - NLM
STAT- MEDLINE
DCOM- 20071109
LR  - 20161124
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 81
IP  - 5
DP  - 2007 May
TI  - Relaxin-induced matrix metalloproteinase-9 expression is associated with 
      activation of the NF-kappaB pathway in human THP-1 cells.
PG  - 1303-10
AB  - Matrix metalloproteinases (MMPs) and relaxin (RLX) are reported to play an 
      important role in tissue remodeling and wound repair. When macrophages populate 
      wound sites, they secrete biologically active substances, including MMPs. The 
      transcription factor NF-kappaB is important in MMP gene regulation in macrophage 
      cells. Thus, a monocyte/macrophage cell line, THP-1, was used to study the 
      molecular mechanism of RLX action on MMP-2 and MMP-9 expression. After 24 h 
      incubation with porcine RLX (100 ng/ml), conditioned media (CM) and THP-1 cells 
      were collected. Gelatin zymography demonstrated an increase in pro-MMP-9 activity 
      in response to RLX in CM, and no significant change in pro-MMP-2 expression was 
      observed. Immunoblot analysis also revealed an increase in pro-MMP-9 in CM from 
      RLX-treated THP-1 cells. Gel EMSA showed that NF-kappaB DNA-binding activity was 
      elevated in THP-1 cells treated with RLX for 10 min and reached a peak at 30 min. 
      The NF-kappaB DNA complex was supershifted using antibodies against NF-kappaB 
      subunits p50 and p65. Increased expression of the p50 and p65 NF-kappaB subunits 
      was also detected in THP-1 cells after RLX treatment. Incubation with RLX (90 
      min) reduced THP-1 expression of the NF-kappaB inhibitor protein, IkappaB-alpha. 
      Using a specific NF-kappaB inhibitor, pyrrolidine dithiocarmate (PDTC) inhibited 
      nuclear binding of NF-kappaB. Pre-exposure to PDTC suppressed pro-MMP-9 activity 
      and protein levels in RLX-treated THP-1 cells. In conclusion, these data suggest 
      that RLX-induced tissue remodeling through increasing MMP-9 expression is 
      dependent on NF-kappaB activation.
FAU - Ho, Teh-Yuan
AU  - Ho TY
AD  - Department of Animal Sciences, Rutgers University, New Brunswick, NJ 08901-8525, 
      USA.
FAU - Yan, Wenbo
AU  - Yan W
FAU - Bagnell, Carol A
AU  - Bagnell CA
LA  - eng
PT  - Journal Article
DEP - 20070208
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Thiocarbamates)
RN  - 135467-92-4 (prolinedithiocarbamate)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 9002-69-1 (Relaxin)
RN  - 9007-49-2 (DNA)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Binding Sites
MH  - Cell Line
MH  - DNA/immunology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - I-kappa B Proteins/antagonists & inhibitors/biosynthesis
MH  - Matrix Metalloproteinase 9/*biosynthesis/*drug effects/immunology
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*drug effects/*immunology
MH  - Proline/analogs & derivatives/pharmacology
MH  - Relaxin/antagonists & inhibitors/*pharmacology
MH  - Signal Transduction/*drug effects/immunology
MH  - Structure-Activity Relationship
MH  - Thiocarbamates/pharmacology
MH  - Time Factors
EDAT- 2007/02/10 09:00
MHDA- 2007/11/10 09:00
CRDT- 2007/02/10 09:00
PHST- 2007/02/10 09:00 [pubmed]
PHST- 2007/11/10 09:00 [medline]
PHST- 2007/02/10 09:00 [entrez]
AID - jlb.0906556 [pii]
AID - 10.1189/jlb.0906556 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2007 May;81(5):1303-10. doi: 10.1189/jlb.0906556. Epub 2007 Feb 8.