PMID- 22544759
OWN - NLM
STAT- MEDLINE
DCOM- 20130115
LR  - 20220331
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 56
IP  - 5
DP  - 2012 Nov
TI  - CD11b(+) Gr1(+) bone marrow cells ameliorate liver fibrosis by producing 
      interleukin-10 in mice.
PG  - 1902-12
LID - 10.1002/hep.25817 [doi]
AB  - Clinical trials and animal models suggest that infusion of bone marrow cells 
      (BMCs) is effective therapy for liver fibrosis, but the underlying mechanisms are 
      obscure, especially those associated with early effects of BMCs. Here, we 
      analyzed the early impact of BMC infusion and identified the subsets of BMCs 
      showing antifibrotic effects in mice with carbon tetrachloride-induced liver 
      fibrosis. An interaction between BMCs and activated hepatic stellate cells (HSCs) 
      was investigated using an in vitro coculturing system. Within 24 hours, infused 
      BMCs were in close contact with activated HSCs, which was associated with reduced 
      liver fibrosis, enhanced hepatic expression of interleukin (IL)-10, and expanded 
      regulatory T cells but decreased macrophage infiltration in the liver at 24 hours 
      after BMC infusion. In contrast, IL-10-deficient (IL-10(-/-) ) BMCs failed to 
      reproduce these effects in fibrotic livers. Intriguingly, in isolated cells, 
      CD11b(+) Gr1(high) F4/80(-) and CD11b(+) Gr1(+) F4/80(+) BMCs expressed more 
      IL-10 after coculturing with activated HSCs, leading to suppressed expression of 
      collagen and alpha-smooth muscle actin in HSCs. Moreover, these effects were either 
      enhanced or abrogated, respectively, when BMCs were cocultured with IL-6(-/-) and 
      retinaldehyde dehydrogenase 1(-/-) HSCs. Similar to murine data, human BMCs 
      expressed more IL-10 after coculturing with human HSC lines (LX-2 or hTERT), and 
      serum IL-10 levels were significantly elevated in patients with liver cirrhosis 
      after autologous BMC infusion. CONCLUSION: Activated HSCs increase IL-10 
      expression in BMCs (CD11b(+) Gr1(high) F4/80(-) and CD11b(+) Gr1(+) F4/80(+) 
      cells), which in turn ameliorates liver fibrosis. Our findings could enhance the 
      design of BMC therapy for liver fibrosis.
CI  - Copyright (c) 2012 American Association for the Study of Liver Diseases.
FAU - Suh, Yang-Gun
AU  - Suh YG
AD  - Graduate School of Medical Science and Engineering, Korea Advanced Institute of 
      Science and Technology, Daejeon, Korea.
FAU - Kim, Ja Kyung
AU  - Kim JK
FAU - Byun, Jin-Seok
AU  - Byun JS
FAU - Yi, Hyon-Seung
AU  - Yi HS
FAU - Lee, Young-Sun
AU  - Lee YS
FAU - Eun, Hyuk Soo
AU  - Eun HS
FAU - Kim, So Yeon
AU  - Kim SY
FAU - Han, Kwang-Hyub
AU  - Han KH
FAU - Lee, Kwan Sik
AU  - Lee KS
FAU - Duester, Gregg
AU  - Duester G
FAU - Friedman, Scott L
AU  - Friedman SL
FAU - Jeong, Won-Il
AU  - Jeong WI
LA  - eng
GR  - R01 DK056621/DK/NIDDK NIH HHS/United States
GR  - R56 DK056621/DK/NIDDK NIH HHS/United States
GR  - R01DK56621/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121009
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Actins)
RN  - 0 (CD11b Antigen)
RN  - 0 (CD4 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Collagen Type I)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (Gr-1 protein, mouse)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (alpha-smooth muscle actin, mouse)
RN  - 130068-27-8 (Interleukin-10)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Bone Marrow Cells/immunology/*metabolism
MH  - Bone Marrow Transplantation
MH  - CD11b Antigen/metabolism
MH  - CD4 Antigens/metabolism
MH  - Carbon Tetrachloride
MH  - Cell Communication
MH  - Chemokine CCL2/genetics/metabolism
MH  - Collagen Type I/metabolism
MH  - Forkhead Transcription Factors/metabolism
MH  - Hepatic Stellate Cells/immunology/*metabolism
MH  - Humans
MH  - Interleukin-1/genetics/metabolism
MH  - Interleukin-10/immunology/*metabolism
MH  - Interleukin-2 Receptor alpha Subunit/metabolism
MH  - Liver Cirrhosis/chemically induced/*immunology/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Nude
MH  - Mice, Transgenic
MH  - RNA, Messenger/metabolism
MH  - Receptors, Chemokine/metabolism
MH  - Statistics, Nonparametric
MH  - T-Lymphocytes, Regulatory/*immunology/metabolism
MH  - Transforming Growth Factor beta1/genetics/metabolism
PMC - PMC3427419
MID - NIHMS374490
EDAT- 2012/05/01 06:00
MHDA- 2013/01/16 06:00
PMCR- 2013/11/01
CRDT- 2012/05/01 06:00
PHST- 2012/02/10 00:00 [received]
PHST- 2012/04/25 00:00 [accepted]
PHST- 2012/05/01 06:00 [entrez]
PHST- 2012/05/01 06:00 [pubmed]
PHST- 2013/01/16 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - 10.1002/hep.25817 [doi]
PST - ppublish
SO  - Hepatology. 2012 Nov;56(5):1902-12. doi: 10.1002/hep.25817. Epub 2012 Oct 9.