PMID- 23732617
OWN - NLM
STAT- MEDLINE
DCOM- 20140211
LR  - 20180822
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Linking)
VI  - 91
IP  - 6
DP  - 2013 Jul
TI  - Nitric oxide inhibits CXCL12 expression in neuroinflammation.
PG  - 427-34
LID - 10.1038/icb.2013.23 [doi]
AB  - Chemokine CXCL12 (C-X-C motif chemokine ligand 12) restricts immune cell invasion 
      of the central nervous system (CNS) and limits neuroinflammation in experimental 
      autoimmune encephalomyelitis (EAE), an animal model of inflammatory and 
      demyelinating disease of the CNS, multiple sclerosis (MS). Nitric oxide (NO), by 
      contrast, predominantly contributes to CNS tissue destruction in MS and EAE. 
      Thus, the influence of NO on CXCL12 in the inflamed CNS was investigated. Excess 
      expression of inducible NO synthase was inversely correlated to CXCL12 gene 
      expression in spinal cord homogenates of rats immunized to develop EAE. NO 
      inhibited gene expression of CXCL12 in astrocytes and endothelial cells in vitro. 
      The inhibition was paralleled with reduction of p38 mitogen-activated protein 
      kinase (MAPK) phosphorylation and it was mimicked with inhibitors of p38 MAPK 
      activation in astrocytes. In vivo suppression of nitric generation recovered 
      CXCL12 expression in the CNS and attenuated EAE in Dark Agouti rats. On the 
      contrary, in vivo NO donation decreased CXCL12 expression in the CNS of 
      EAE-resistant Albino Oxford (AO) rats. However, the effect was not paralleled 
      with induction of EAE in AO rats. It is suggested that NO acting through 
      suppression of p38 MAPK inhibits CXCL12 expression in neuroinflammation. These 
      results imply that downregulation of NO release and protection of CXCL12 
      expression within the CNS might present the potential approaches in MS therapy.
FAU - Petkovic, Filip
AU  - Petkovic F
AD  - Department of Immunology, Institute for Biological Research, Sinisa Stankovic, 
      University of Belgrade, Belgrade, Serbia.
FAU - Blazevski, Jana
AU  - Blazevski J
FAU - Momcilovic, Miljana
AU  - Momcilovic M
FAU - Mostarica Stojkovic, Marija
AU  - Mostarica Stojkovic M
FAU - Miljkovic, Djordje
AU  - Miljkovic D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130604
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (CXCL12 protein, rat)
RN  - 0 (Chemokine CXCL12)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Astrocytes/immunology
MH  - Chemokine CXCL12/*antagonists & inhibitors/biosynthesis
MH  - Disease Models, Animal
MH  - Encephalomyelitis, Autoimmune, Experimental/*immunology/therapy
MH  - Endothelial Cells/*immunology
MH  - Humans
MH  - Immunotherapy/methods/trends
MH  - Multiple Sclerosis/*immunology/therapy
MH  - Nitric Oxide/*immunology
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2013/06/05 06:00
MHDA- 2014/02/12 06:00
CRDT- 2013/06/05 06:00
PHST- 2013/01/21 00:00 [received]
PHST- 2013/05/07 00:00 [revised]
PHST- 2013/05/08 00:00 [accepted]
PHST- 2013/06/05 06:00 [entrez]
PHST- 2013/06/05 06:00 [pubmed]
PHST- 2014/02/12 06:00 [medline]
AID - icb201323 [pii]
AID - 10.1038/icb.2013.23 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2013 Jul;91(6):427-34. doi: 10.1038/icb.2013.23. Epub 2013 Jun 
      4.