PMID- 21868490
DCOM- 20120713
LR  - 20171116
IS  - 1468-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 61
IP  - 6
DP  - 2012 Jun
TI  - Bone marrow transplantation improves hepatic fibrosis in Abcb4-/- mice via Th1
      response and matrix metalloproteinase activity.
PG  - 907-16
LID - 10.1136/gutjnl-2011-300608 [doi]
AB  - OBJECTIVE: Reports on the effects of bone marrow-derived cells on hepatic
      fibrosis are contradictory. Impaired fibrosis but increased inflammation has
      recently been demonstrated 10 weeks after bone marrow transplantation (BM-Tx) in 
      Abcb4-/- mice. It is hypothesised that BM-Tx might have long-term therapeutic
      potential by altering the immunological and matrix remodelling processes leading 
      to hepatic regeneration. METHODS: After lethal irradiation of recipient mice, BM 
      cells from GFP+ donor mice (allogeneic Tx) or Abcb4-/- mice (syngeneic Tx) were
      transplanted via tail vein injection. Readouts were performed 2, 10 and 20 weeks 
      after Tx. Liver integrity was assessed serologically and histologically.
      Surrogate markers for fibrogenesis, T helper (Th) response, inflammation,
      graft-versus-host disease and fibrolysis were analysed by quantitative real-time 
      PCR, zymography and immunohistology. RESULTS: 20 weeks after syngeneic and
      allogeneic BM-Tx, hepatic grading and staging were significantly improved. In
      contrast, 2 weeks after BM-Tx inflammatory grading, expression of inflammatory
      cell markers and associated chemokines and their receptors were increased and
      subsequently declined. In parallel, CD8+/GFP+ donor-derived T cells infiltrated
      the liver 2 weeks after BM-Tx. The Th1 cyokine interferon gamma was increased 2
      and 10 weeks after BM-Tx whereas the Th2 associated interleukin 13 was not
      altered. The gene expression of matrix metalloproteinases MMP-2, MMP-7, MMP-9 and
      MMP-13 was transiently upregulated and MMP-9 protein remained elevated 20 weeks
      after BM-Tx with enhanced gelatinase activity located within the fibrotic areas. 
      Neutrophils were identified as major sources of MMP-9. CONCLUSION: These results 
      show that BM-Tx causes an antifibrotic Th1 response combined with transient
      inflammatory effects and subsequently upregulated MMP activity. Antifibrotic Th
      polarisation and prolonged proteolytic activity, especially of MMP-9, might be
      responsible for long-term amelioration of hepatic fibrosis.
FAU - Roderfeld, Martin
AU  - Roderfeld M
AD  - Department of Gastroenterology, Justus-Liebig-University Giessen, Giessen,
FAU - Rath, Timo
AU  - Rath T
FAU - Pasupuleti, Sravanthi
AU  - Pasupuleti S
FAU - Zimmermann, Marc
AU  - Zimmermann M
FAU - Neumann, Caterina
AU  - Neumann C
FAU - Churin, Yuri
AU  - Churin Y
FAU - Dierkes, Christian
AU  - Dierkes C
FAU - Voswinckel, Robert
AU  - Voswinckel R
FAU - Barth, Peter J
AU  - Barth PJ
FAU - Zahner, Daniel
AU  - Zahner D
FAU - Graf, Jurgen
AU  - Graf J
FAU - Roeb, Elke
AU  - Roeb E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110825
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (ATP Binding Cassette Transporter, Sub-Family B)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (P-glycoprotein 2)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC (Matrix Metalloproteinase 9)
SB  - IM
MH  - ATP Binding Cassette Transporter, Sub-Family B/*physiology
MH  - Animals
MH  - Bone Marrow Transplantation/*methods
MH  - Chemokines/metabolism
MH  - Cytokines/metabolism
MH  - Interferon-gamma/metabolism
MH  - Liver/pathology
MH  - Liver Cirrhosis/enzymology/metabolism/pathology/*therapy
MH  - Matrix Metalloproteinase 9/metabolism/physiology
MH  - Matrix Metalloproteinases/*metabolism/physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Th1 Cells/*physiology
EDAT- 2011/08/27 06:00
MHDA- 2012/07/14 06:00
CRDT- 2011/08/27 06:00
PHST- 2011/08/27 06:00 [entrez]
PHST- 2011/08/27 06:00 [pubmed]
PHST- 2012/07/14 06:00 [medline]
AID - gutjnl-2011-300608 [pii]
AID - 10.1136/gutjnl-2011-300608 [doi]
PST - ppublish
SO  - Gut. 2012 Jun;61(6):907-16. doi: 10.1136/gutjnl-2011-300608. Epub 2011 Aug 25.