PMID- 22851861
OWN - NLM
STAT- MEDLINE
DCOM- 20130110
LR  - 20211021
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Print)
IS  - 1007-9327 (Linking)
VI  - 18
IP  - 28
DP  - 2012 Jul 28
TI  - Lentiviral vector-mediated down-regulation of IL-17A receptor in hepatic stellate 
      cells results in decreased secretion of IL-6.
PG  - 3696-704
LID - 10.3748/wjg.v18.i28.3696 [doi]
AB  - AIM: To investigate the mechanism of interleukin (IL)-6 secretion through 
      blocking the IL-17A/IL-17A receptor (IL-17RA) signaling pathway with a short 
      hairpin RNA (shRNA) in hepatic stellate cells (HSCs) in vitro. METHODS: HSCs were 
      derived from the livers of adult male Sprague-Dawley rats. IL-6 expression was 
      evaluated using real-time quantitative polymerase chain reaction and enzyme 
      linked immunosorbent assay. The phosphorylation activity of p38 mitogen activated 
      protein kinases (MAPK) and extracellular regulated protein kinases (ERK) 1/2 upon 
      induction by IL-17A and suppression by IL-17RA shRNA were examined using Western 
      blotting. RESULTS: IL-6 expression induced by IL-17A was significantly increased 
      compared to control in HSCs (P < 0.01 in a dose-dependent manner). Suppression of 
      IL-17RA using lentiviral-mediated shRNA inhibited IL-6 expression induced by 
      IL-17A compared to group with only IL-17A treatment (1.44 +/- 0.17 vs 4.07 +/- 0.43, 
      P < 0.01). IL-17A induced rapid phosphorylation of p38 MAPK and ERK1/2 after 5 
      min exposure, and showed the strongest levels of phosphorylation of p38 MAPK and 
      ERK1/2 at 15 min in IL-17A-treated HSCs. IL-6 mRNA expression induced by IL-17A 
      (100 ng/mL) for 3 h exposure was inhibited by preincubation with specific 
      inhibitors of p38 MAPK (SB-203580) and ERK1/2 (PD-98059) compared to groups 
      without inhibitors preincubation (1.67 +/- 0.24, 2.01 +/- 0.10 vs 4.08 +/- 0.59, P < 
      0.01). Moreover, Lentiviral-mediated IL-17RA shRNA 1 inhibited IL-17A-induced 
      IL-6 mRNA expression compared to random shRNA in HSCs (1.44 +/- 0.17 vs 3.98 +/- 
      0.68, P < 0.01). Lentiviral-mediated IL-17RA shRNA 1 inhibited phosphorylation of 
      p38 MAPK and ERK1/2 induced by 15 min IL-17A (100 ng/mL) exposure. CONCLUSION: 
      Down-regulation of the IL-17RA receptor by shRNA decreased IL-6 expression 
      induced by IL-17A via p38 MAPK and ERK1/2 phosphorylation in HSCs. Suppression of 
      IL-17RA expression may be a strategy to reduce the inflammatory response induced 
      by IL-17A in the liver.
FAU - Zhang, Sheng-Chu
AU  - Zhang SC
AD  - Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical 
      College, Wenzhou 325000, Zhejiang Province, China.
FAU - Zheng, Yi-Hu
AU  - Zheng YH
FAU - Yu, Pan-Pan
AU  - Yu PP
FAU - Min, Tan Hooi
AU  - Min TH
FAU - Yu, Fu-Xiang
AU  - Yu FX
FAU - Ye, Chao
AU  - Ye C
FAU - Xie, Yuan-Kang
AU  - Xie YK
FAU - Zhang, Qi-Yu
AU  - Zhang QY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Interleukin-17)
RN  - EC 2.7.11.24 (Mapk1 protein, rat)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - *Gene Expression Regulation
MH  - Genetic Vectors
MH  - Hepatic Stellate Cells/*cytology
MH  - Inflammation
MH  - Interleukin-6/*metabolism
MH  - Lentivirus/*genetics
MH  - Liver Cirrhosis/pathology
MH  - Male
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Plasmids/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Interleukin-17/*metabolism
MH  - Signal Transduction
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC3406421
OTO - NOTNLM
OT  - Hepatic stellate cells
OT  - Interleukin 17A
OT  - Interleukin 6
OT  - Liver fibrosis
EDAT- 2012/08/02 06:00
MHDA- 2013/01/11 06:00
PMCR- 2012/07/28
CRDT- 2012/08/02 06:00
PHST- 2011/10/05 00:00 [received]
PHST- 2012/04/04 00:00 [revised]
PHST- 2012/05/06 00:00 [accepted]
PHST- 2012/08/02 06:00 [entrez]
PHST- 2012/08/02 06:00 [pubmed]
PHST- 2013/01/11 06:00 [medline]
PHST- 2012/07/28 00:00 [pmc-release]
AID - 10.3748/wjg.v18.i28.3696 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2012 Jul 28;18(28):3696-704. doi: 
      10.3748/wjg.v18.i28.3696.