PMID- 26118387
OWN - NLM
STAT- MEDLINE
DCOM- 20160727
LR  - 20171116
IS  - 1205-7541 (Electronic)
IS  - 0008-4212 (Linking)
VI  - 93
IP  - 7
DP  - 2015 Jul
TI  - Homocysteine elicits an M1 phenotype in murine macrophages through an 
      EMMPRIN-mediated pathway.
PG  - 577-84
LID - 10.1139/cjpp-2014-0520 [doi]
AB  - INTRODUCTION: Hyperhomocysteinemia (HHcy) is associated with inflammatory 
      diseases and is known to increase the production of reactive oxygen species 
      (ROS), matrix metalloproteinase (MMP)-9, and inducible nitric oxide synthase, and 
      to decrease endothelial nitric oxide production. However, the impact of HHcy on 
      macrophage phenotype differentiation is not well-established. It has been 
      documented that macrophages have 2 distinct phenotypes: the "classically 
      activated/destructive" (M1), and the "alternatively activated/constructive" (M2) 
      subtypes. We hypothesize that HHcy increases M1 macrophage differentiation 
      through extracellular matrix metalloproteinase inducer (EMMPRIN), a known inducer 
      of matrix metalloproteinases. METHODS: murine J774A.1 and Raw 264.7 macrophages 
      were treated with 100 and 500 mumol/L Hcy, respectively, for 24 h. Samples were 
      analyzed using Western blotting and immunocytochemistry. RESULTS: Homocysteine 
      treatment increased cluster of differentiation 40 (CD40; M1 marker) in J774A.1 
      and Raw 264.7 macrophages. MMP-9 was induced in both cell lines. EMMPRIN protein 
      expression was also increased in both cell lines. Blocking EMMPRIN function by 
      pre-treating cells with anti-EMMPRIN antibody, with or without Hcy, resulted in 
      significantly lower expression of CD40 in both cell lines by comparison with the 
      controls. A DCFDA assay demonstrated increased ROS production in both cell lines 
      with Hcy treatment when compared with the controls. CONCLUSION: Our results 
      suggest that HHcy results in an increase of the M1 macrophage phenotype. This 
      effect seems to be at least partially mediated by EMMPRIN induction.
FAU - Winchester, Lee J
AU  - Winchester LJ
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, 500 South Preston Street, HSC Building A, KY 40202, USA.
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, 500 South Preston Street, HSC Building A, KY 40202, USA.
FAU - Veeranki, Sudhakar
AU  - Veeranki S
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, 500 South Preston Street, HSC Building A, KY 40202, USA.
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, 500 South Preston Street, HSC Building A, KY 40202, USA.
FAU - Givvimani, Srikanth
AU  - Givvimani S
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, 500 South Preston Street, HSC Building A, KY 40202, USA.
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, 500 South Preston Street, HSC Building A, KY 40202, USA.
FAU - Tyagi, Suresh C
AU  - Tyagi SC
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, 500 South Preston Street, HSC Building A, KY 40202, USA.
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, 500 South Preston Street, HSC Building A, KY 40202, USA.
LA  - eng
GR  - HL- 74185/HL/NHLBI NIH HHS/United States
GR  - HL-10864/HL/NHLBI NIH HHS/United States
GR  - NS-084823/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150331
PL  - Canada
TA  - Can J Physiol Pharmacol
JT  - Canadian journal of physiology and pharmacology
JID - 0372712
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Bsg protein, mouse)
RN  - 0 (CD40 Antigens)
RN  - 0 (Reactive Oxygen Species)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 136894-56-9 (Basigin)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Basigin/*biosynthesis
MH  - Blotting, Western
MH  - CD40 Antigens/biosynthesis
MH  - Cell Culture Techniques
MH  - Cell Differentiation/*drug effects
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - Homocysteine/*pharmacology
MH  - Immunohistochemistry
MH  - Macrophages/*drug effects/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - EMMPRIN
OT  - M1
OT  - MMP-9
OT  - ROS
OT  - derives reactifs de l'oxygene
OT  - homocysteine
OT  - homocysteine
OT  - macrophage
OT  - metalloproteinase matricielle-9
EDAT- 2015/06/30 06:00
MHDA- 2016/07/28 06:00
CRDT- 2015/06/30 06:00
PHST- 2015/06/30 06:00 [entrez]
PHST- 2015/06/30 06:00 [pubmed]
PHST- 2016/07/28 06:00 [medline]
AID - 10.1139/cjpp-2014-0520 [doi]
PST - ppublish
SO  - Can J Physiol Pharmacol. 2015 Jul;93(7):577-84. doi: 10.1139/cjpp-2014-0520. Epub 
      2015 Mar 31.