PMID- 28238855
OWN - NLM
STAT- MEDLINE
DCOM- 20180119
LR  - 20220316
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 34
DP  - 2017 Jun
TI  - MKP-1 negatively regulates LPS-mediated IL-1beta production through p38 activation 
      and HIF-1alpha expression.
PG  - 1-10
LID - S0898-6568(17)30058-X [pii]
LID - 10.1016/j.cellsig.2017.02.018 [doi]
AB  - Interleukin 1 beta (IL-1beta) is a pro-inflammatory cytokine that plays a major role 
      in inflammatory diseases as well as cancer. The inflammatory response after 
      Toll-like receptor (TLR) 4 activation is tightly regulated through 
      phosphorylation of MAP kinases, including p38 and JNK pathways. The activation of 
      MAP kinases is negatively regulated by MAPK phosphatases (MKPs). MKP-1 
      preferentially dephosphorylates p38 and JNK. IL-1beta is regulated through the 
      activation of MAPK, including p38 as well as several transcription factors. The 
      oxygen-sensitive transcription factor HIF-1alpha is a known transcription factor for 
      several inflammatory cytokines including IL-1beta and IL-6. Here, we report that 
      MKP-1 regulates HIF-1alpha expression in response to LPS. MKP-1 deficient bone marrow 
      derived macrophages (BMDMs) exhibited increased reactive oxygen species (ROS) 
      production and higher HIF-1alpha expression. In contrast, the expression of all three 
      isoforms of prolyl hydroxylases (PHDs), which are important in destabilizing 
      HIF-1alpha through hydroxylation, were significantly decreased in MKP-1 deficient 
      BMDMs. LPS challenge of MKP-1 deficient BMDMs led to a substantial increase in 
      IL-1beta production. An inhibitor of HIF-1alpha significantly decreased LPS mediated 
      IL-1beta production both at the transcript and protein levels. Similarly, inhibition 
      of p38 MAP kinase reduced LPS mediated pro-IL-1beta and HIF-1alpha protein levels as 
      well as ROS production in MKP-1 deficient BMDMs. These findings demonstrate a 
      regulatory function for MKP-1 in modulating IL-1beta expression through p38 
      activation, ROS production and HIF-1alpha expression.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Talwar, Harvinder
AU  - Talwar H
AD  - Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, 
      Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 
      48201, USA.
FAU - Bauerfeld, Christian
AU  - Bauerfeld C
AD  - Department of Pediatrics, Division of Critical Care, Wayne State University 
      School of Medicine and Detroit Medical Center, Detroit, MI 48201, USA.
FAU - Bouhamdan, Mohamad
AU  - Bouhamdan M
AD  - Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, 
      Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 
      48201, USA.
FAU - Farshi, Pershang
AU  - Farshi P
AD  - Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, 
      Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 
      48201, USA.
FAU - Liu, Yusen
AU  - Liu Y
AD  - Center for Perinatal Research, The Research Institute at Nationwide Children's 
      Hospital, Columbus, OH 43205, USA; Department of Pediatrics, The Ohio State 
      University College of Medicine, USA.
FAU - Samavati, Lobelia
AU  - Samavati L
AD  - Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, 
      Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 
      48201, USA; Center for Molecular Medicine and Genetics, Wayne State University 
      School of Medicine, Detroit, MI 48201, USA. Electronic address: ay6003@wayne.edu.
LA  - eng
GR  - R01 AI124029/AI/NIAID NIH HHS/United States
GR  - R01 HL113508/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170224
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Anthracenes)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Reactive Oxygen Species)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - 512-64-1 (Echinomycin)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 1)
RN  - EC 3.1.3.48 (Dusp1 protein, mouse)
SB  - IM
EIN - Cell Signal. 2017 Oct;38:239. PMID: 28619580
MH  - Animals
MH  - Anthracenes/pharmacology
MH  - Dual Specificity Phosphatase 1/deficiency/genetics/*metabolism
MH  - Echinomycin/pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Interleukin-1beta/analysis/genetics/metabolism
MH  - Interleukin-6/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Macrophages/cytology/drug effects/metabolism
MH  - Mice
MH  - Phosphorylation/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
PMC - PMC5410178
MID - NIHMS855827
OTO - NOTNLM
OT  - BMDMs
OT  - DUSPs
OT  - HIF-1 alpha
OT  - IL-1beta
OT  - MKP-1
OT  - Macrophages
OT  - p38
COIS- Conflict of interest The authors declare that no conflict of interest exists.
EDAT- 2017/02/28 06:00
MHDA- 2018/01/20 06:00
PMCR- 2018/06/01
CRDT- 2017/02/28 06:00
PHST- 2016/12/04 00:00 [received]
PHST- 2017/02/13 00:00 [revised]
PHST- 2017/02/20 00:00 [accepted]
PHST- 2017/02/28 06:00 [pubmed]
PHST- 2018/01/20 06:00 [medline]
PHST- 2017/02/28 06:00 [entrez]
PHST- 2018/06/01 00:00 [pmc-release]
AID - S0898-6568(17)30058-X [pii]
AID - 10.1016/j.cellsig.2017.02.018 [doi]
PST - ppublish
SO  - Cell Signal. 2017 Jun;34:1-10. doi: 10.1016/j.cellsig.2017.02.018. Epub 2017 Feb 
      24.