PMID- 26901653
OWN - NLM
STAT- MEDLINE
DCOM- 20160718
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 2
DP  - 2016
TI  - SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by 
      Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation.
PG  - e0149486
LID - 10.1371/journal.pone.0149486 [doi]
LID - e0149486
AB  - Dengue virus (DENV) infection causes organ injuries, and the liver is one of the 
      most important sites of DENV infection, where viral replication generates a high 
      viral load. The molecular mechanism of DENV-induced liver injury is still under 
      investigation. The mitogen activated protein kinases (MAPKs), including p38 MAPK, 
      have roles in the hepatic cell apoptosis induced by DENV. However, the in vivo 
      role of p38 MAPK in DENV-induced liver injury is not fully understood. In this 
      study, we investigated the role of SB203580, a p38 MAPK inhibitor, in a mouse 
      model of DENV infection. Both the hematological parameters, leucopenia and 
      thrombocytopenia, were improved by SB203580 treatment and liver transaminases and 
      histopathology were also improved. We used a real-time PCR microarray to profile 
      the expression of apoptosis-related genes. Tumor necrosis factor alpha, caspase 9, 
      caspase 8, and caspase 3 proteins were significantly lower in the 
      SB203580-treated DENV-infected mice than that in the infected control mice. 
      Increased expressions of cytokines including TNF-alpha, IL-6 and IL-10, and 
      chemokines including RANTES and IP-10 in DENV infection were reduced by SB203580 
      treatment. DENV infection induced the phosphorylation of p38MAPK, and its 
      downstream signals including MAPKAPK2, HSP27 and ATF-2. SB203580 treatment did 
      not decrease the phosphorylation of p38 MAPK, but it significantly reduced the 
      phosphorylation of MAPKAPK2, HSP27, and ATF2. Therefore, SB203580 modulates the 
      downstream signals to p38 MAPK and reduces DENV-induced liver injury.
FAU - Sreekanth, Gopinathan Pillai
AU  - Sreekanth GP
AD  - Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, 
      Bangkok, Thailand.
FAU - Chuncharunee, Aporn
AU  - Chuncharunee A
AD  - Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, 
      Bangkok, Thailand.
FAU - Sirimontaporn, Aunchalee
AU  - Sirimontaporn A
AD  - Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, 
      Bangkok, Thailand.
FAU - Panaampon, Jutatip
AU  - Panaampon J
AD  - Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, 
      Bangkok, Thailand.
FAU - Noisakran, Sansanee
AU  - Noisakran S
AD  - Medical Biotechnology Unit, National Center for Genetic Engineering and 
      Biotechnology, National Science and Technology Development Agency, Bangkok, 
      Thailand.
FAU - Yenchitsomanus, Pa-Thai
AU  - Yenchitsomanus PT
AD  - Division of Molecular Medicine, Department of Research and Development, Faculty 
      of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
FAU - Limjindaporn, Thawornchai
AU  - Limjindaporn T
AD  - Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, 
      Bangkok, Thailand.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160222
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Activating Transcription Factor 2)
RN  - 0 (HSP27 Heat-Shock Proteins)
RN  - 0 (Imidazoles)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Pyridines)
RN  - EC 2.7.1.- (MAP-kinase-activated kinase 2)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Activating Transcription Factor 2/*metabolism
MH  - Animals
MH  - Dengue Virus/*pathogenicity
MH  - HSP27 Heat-Shock Proteins/*metabolism
MH  - Imidazoles/*therapeutic use
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Liver/drug effects/injuries/virology
MH  - Liver Diseases/*drug therapy/virology
MH  - MAP Kinase Signaling System/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Phosphorylation/drug effects
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Pyridines/*therapeutic use
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC4764010
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/02/24 06:00
MHDA- 2016/07/19 06:00
PMCR- 2016/02/22
CRDT- 2016/02/23 06:00
PHST- 2015/11/04 00:00 [received]
PHST- 2016/02/02 00:00 [accepted]
PHST- 2016/02/23 06:00 [entrez]
PHST- 2016/02/24 06:00 [pubmed]
PHST- 2016/07/19 06:00 [medline]
PHST- 2016/02/22 00:00 [pmc-release]
AID - PONE-D-15-48049 [pii]
AID - 10.1371/journal.pone.0149486 [doi]
PST - epublish
SO  - PLoS One. 2016 Feb 22;11(2):e0149486. doi: 10.1371/journal.pone.0149486. 
      eCollection 2016.