PMID- 25847238
OWN - NLM
STAT- MEDLINE
DCOM- 20150729
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 290
IP  - 20
DP  - 2015 May 15
TI  - Hepatic serum amyloid A1 aggravates T cell-mediated hepatitis by inducing 
      chemokines via Toll-like receptor 2 in mice.
PG  - 12804-11
LID - 10.1074/jbc.M114.635763 [doi]
AB  - Serum amyloid A is a proinflammatory molecule that induces leukocyte infiltration 
      and promotes neutrophil adhesion to endothelial cells under inflammatory 
      conditions. The aim of this study was to examine whether Saa1 aggravates T 
      cell-mediated hepatitis by inducing chemokines in a liver-specific, 
      Saa1-overexpressing, transgenic (TG) mouse model. We generated TG mice in which 
      Saa1 was overexpressed specifically in liver tissue. The chemokines monocyte 
      chemotactic protein 1 (MCP1), MIP1alpha, MIP1beta, interferon gamma-induced protein 10 
      (IP-10), and eotaxin were induced in Saa1 TG mice. After concanavalin A 
      treatment, Saa1 expression was higher in Saa1 TG mice than in WT mice. More 
      severe liver injury, increased hepatocyte apoptosis, and higher levels of hepatic 
      enzymes were observed in Saa1 TG mice than in WT mice. Liver infiltration of 
      CD4(+) T cells and macrophages increased after inducing hepatitis. Activation of 
      T cells was higher in Saa1 TG mice than in WT mice, and the populations of Th17 
      cells and regulatory T cells were altered by overexpressing Saa1 in TG mice. 
      Secretion of various cytokines, such as interferon gamma, tumor necrosis factor alpha, 
      and interleukin 6, increased in Saa1 TG mice. Injecting a Toll-like receptor 2 
      (TLR2) antagonist in vivo inhibited chemokine expression and IkappaBalpha phosphorylation 
      and showed that the induction of chemokines by Saa1 was dependent on TLR2. 
      Hepatic Saa1 accelerated T cell-mediated hepatitis by inducing chemokine 
      production and activating T cells by TLR2. Therefore, Saa1 might be a novel 
      inflammatory factor that acts as a chemokine modulator in hepatitis.
CI  - (c) 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Ji, Young Rae
AU  - Ji YR
AD  - From the School of Life Science, KNU Creative BioResearch Group (BK21 Plus 
      Project), Kyungpook National University, Buk-gu, Daegu 702-701, Korea and.
FAU - Kim, Hei Jung
AU  - Kim HJ
AD  - From the School of Life Science, KNU Creative BioResearch Group (BK21 Plus 
      Project), Kyungpook National University, Buk-gu, Daegu 702-701, Korea and.
FAU - Bae, Ki Beom
AU  - Bae KB
AD  - From the School of Life Science, KNU Creative BioResearch Group (BK21 Plus 
      Project), Kyungpook National University, Buk-gu, Daegu 702-701, Korea and.
FAU - Lee, Sanggyu
AU  - Lee S
AD  - From the School of Life Science, KNU Creative BioResearch Group (BK21 Plus 
      Project), Kyungpook National University, Buk-gu, Daegu 702-701, Korea and.
FAU - Kim, Myoung Ok
AU  - Kim MO
AD  - the Department of Animal Science, Kyungpook National University, Sangju 742-711, 
      Korea.
FAU - Ryoo, Zae Young
AU  - Ryoo ZY
AD  - From the School of Life Science, KNU Creative BioResearch Group (BK21 Plus 
      Project), Kyungpook National University, Buk-gu, Daegu 702-701, Korea and 
      jaewoong64@hanmail.net.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150406
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chemokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Mitogens)
RN  - 0 (Saa2 protein, mouse)
RN  - 0 (Serum Amyloid A Protein)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 11028-71-0 (Concanavalin A)
SB  - IM
MH  - Animals
MH  - Chemical and Drug Induced Liver Injury/genetics/*metabolism/pathology
MH  - Chemokines/*biosynthesis/genetics
MH  - Concanavalin A/adverse effects/pharmacology
MH  - Inflammation Mediators/*metabolism
MH  - Liver/metabolism/pathology
MH  - Lymphocyte Activation/drug effects/genetics
MH  - Macrophages/metabolism/pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitogens/adverse effects/pharmacology
MH  - Serum Amyloid A Protein/*biosynthesis/genetics
MH  - T-Lymphocytes, Regulatory/*metabolism/pathology
MH  - Th17 Cells/*metabolism/pathology
MH  - Toll-Like Receptor 2/antagonists & inhibitors/genetics/*metabolism
PMC - PMC4432296
OTO - NOTNLM
OT  - Saa1
OT  - T cell activation
OT  - Toll like receptor
OT  - chemokine
OT  - concanavalin A
OT  - cytokine
OT  - inflammation
OT  - liver injury
OT  - transgenic mice
EDAT- 2015/04/08 06:00
MHDA- 2015/07/30 06:00
PMCR- 2016/05/15
CRDT- 2015/04/08 06:00
PHST- 2014/12/28 00:00 [received]
PHST- 2015/04/08 06:00 [entrez]
PHST- 2015/04/08 06:00 [pubmed]
PHST- 2015/07/30 06:00 [medline]
PHST- 2016/05/15 00:00 [pmc-release]
AID - S0021-9258(20)33748-0 [pii]
AID - M114.635763 [pii]
AID - 10.1074/jbc.M114.635763 [doi]
PST - ppublish
SO  - J Biol Chem. 2015 May 15;290(20):12804-11. doi: 10.1074/jbc.M114.635763. Epub 
      2015 Apr 6.