PMID- 22519363
OWN - NLM
STAT- MEDLINE
DCOM- 20121031
LR  - 20151119
IS  - 1502-7708 (Electronic)
IS  - 0036-5521 (Linking)
VI  - 47
IP  - 7
DP  - 2012 Jul
TI  - Serum MMPs 7-9 and their inhibitors during glucocorticoid and anti-TNF-alpha therapy 
      in pediatric inflammatory bowel disease.
PG  - 785-94
LID - 10.3109/00365521.2012.677954 [doi]
AB  - OBJECTIVES: In inflammatory bowel diseases (IBD), matrix metalloproteinases 
      (MMPs) participate in intestinal tissue damage and regenerative processes. MMP 
      activity is inhibited by tissue inhibitors of MMPs (TIMPs) and plasma inhibitor, 
      alpha(2)-macroglobulin (alpha2M). We evaluated serum MMPs, their inhibitors and markers of 
      neutrophil activity, myeloperoxidase (MPO) and human neutrophil elastase (HNE), 
      during glucocorticoid (GC) and anti-TNF-alpha therapies in pediatric IBD, in aim to 
      find new tools for assessment of therapeutic response. METHODS: Serum samples 
      were collected before and within a month after the start of therapy with oral GC 
      (n = 19) or anti-TNF-alpha agent (n = 16), and from 32 pediatric control patients. 
      Serum levels of MMP-7, MMP-9, TIMP-1, TIMP-2, alpha2M, MPO, and HNE were analyzed 
      with enzyme-linked immunoabsorbent assays (ELISA) and MMP-8 by immunofluorometric 
      assay (IFMA). Disease activity was monitored with erythrocyte sedimentation rate 
      (ESR), CRP, fecal calprotectin (FC), and physician's global assessment of 
      clinical disease activity (PGA). RESULTS: In IBD, pretreatment serum MMP-7, 
      MMP-8, MMP-9, alpha2M, MPO, and HNE were elevated compared with controls. During GC 
      therapy, MMP-7, TIMP-1, and MMP-7/TIMP-2 decreased (all p < 0.05). During 
      anti-TNF-alpha therapy, MMP-7 decreased (p = 0.063), but remained higher than that 
      after GC therapy (p < 0.05). alpha2M (p < 0.05) and HNE (p < 0.05) increased, the 
      former higher than that in GC-treated patients. The levels of MMPs and their 
      inhibitors did not markedly associate with inflammatory markers in blood or 
      feces. CONCLUSIONS: In pediatric IBD, serum MMP-7 mirrors disease activity, and 
      together with TIMP-1, reflects GC therapy response. alpha(2)-Macroglobulin expression 
      parallels the anti-TNF-alpha response.
FAU - Makitalo, Laura
AU  - Makitalo L
AD  - Children's Hospital, Helsinki University Central Hospital and University of 
      Helsinki, Helsinki, Finland. laura.makitalo@helsinki.fi
FAU - Rintamaki, Hanne
AU  - Rintamaki H
FAU - Tervahartiala, Taina
AU  - Tervahartiala T
FAU - Sorsa, Timo
AU  - Sorsa T
FAU - Kolho, Kaija-Leena
AU  - Kolho KL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120423
PL  - England
TA  - Scand J Gastroenterol
JT  - Scandinavian journal of gastroenterology
JID - 0060105
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Glucocorticoids)
RN  - 0 (Leukocyte L1 Antigen Complex)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (alpha-Macroglobulins)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 51333-22-3 (Budesonide)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - 9PHQ9Y1OLM (Prednisolone)
RN  - B72HH48FLU (Infliximab)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
RN  - EC 3.4.24.23 (Matrix Metalloproteinase 7)
RN  - EC 3.4.24.34 (Matrix Metalloproteinase 8)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Adolescent
MH  - Anti-Inflammatory Agents/therapeutic use
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Blood Sedimentation
MH  - Budesonide/therapeutic use
MH  - C-Reactive Protein/metabolism
MH  - Child
MH  - Child, Preschool
MH  - Colitis, Ulcerative/*blood/*drug therapy/pathology
MH  - Crohn Disease/*blood/*drug therapy/pathology
MH  - Feces
MH  - Female
MH  - Glucocorticoids/*therapeutic use
MH  - Humans
MH  - Infliximab
MH  - Leukocyte Elastase/blood
MH  - Leukocyte L1 Antigen Complex/metabolism
MH  - Male
MH  - Matrix Metalloproteinase 7/blood
MH  - Matrix Metalloproteinase 8/blood
MH  - Matrix Metalloproteinase 9/blood
MH  - Peroxidase/blood
MH  - Prednisolone/therapeutic use
MH  - Tissue Inhibitor of Metalloproteinase-1/blood
MH  - Tissue Inhibitor of Metalloproteinase-2/blood
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
MH  - alpha-Macroglobulins/metabolism
EDAT- 2012/04/24 06:00
MHDA- 2012/11/01 06:00
CRDT- 2012/04/24 06:00
PHST- 2012/04/24 06:00 [entrez]
PHST- 2012/04/24 06:00 [pubmed]
PHST- 2012/11/01 06:00 [medline]
AID - 10.3109/00365521.2012.677954 [doi]
PST - ppublish
SO  - Scand J Gastroenterol. 2012 Jul;47(7):785-94. doi: 10.3109/00365521.2012.677954. 
      Epub 2012 Apr 23.