PMID- 30467554
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240306
IS  - 2573-7732 (Print)
IS  - 2573-7732 (Electronic)
IS  - 2573-7732 (Linking)
VI  - 2
IP  - 1
DP  - 2018 Jan 1
TI  - Species-Specific Transcriptional Regulation of Genes Involved in Nitric Oxide 
      Production and Arginine Metabolism in Macrophages.
PG  - 27-37
LID - 10.4049/immunohorizons.1700073 [doi]
AB  - Activated mouse macrophages metabolize arginine via NO synthase (NOS2) to produce 
      NO as an antimicrobial effector. Published gene expression datasets provide 
      little support for the activation of this pathway in human macrophages. 
      Generation of NO requires the coordinated regulation of multiple genes. We have 
      generated RNA-sequencing data from bone marrow-derived macrophages from 
      representative rodent (rat), monogastric (pig and horse), and ruminant (sheep, 
      goat, cattle, and water buffalo) species, and analyzed the expression of genes 
      involved in arginine metabolism in response to stimulation with LPS. In rats, as 
      in mice, LPS strongly induced Nos2, the arginine transporter Slc7a2, arginase 1 
      (Arg1), GTP cyclohydrolase (Gch1), and argininosuccinate synthase (Ass1). None of 
      these responses was conserved across species. Only cattle and water buffalo 
      showed substantial NOS2 induction. The species studied also differed in 
      expression and regulation of arginase (ARG2, rather than ARG1), and amino acid 
      transporters. Variation between species was associated with rapid promoter 
      evolution. Differential induction of NOS2 and ARG2 between the ruminant species 
      was associated with insertions of the Bov-A2 retrotransposon in the promoter 
      region. Bov-A2 was shown to possess LPS-inducible enhancer activity in 
      transfected RAW264.7 macrophages. Consistent with a function in innate immunity, 
      NO production and arginine metabolism vary greatly between species and 
      differences may contribute to pathogen host restriction.
FAU - Young, Rachel
AU  - Young R
AD  - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of 
      Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
FAU - Bush, Stephen J
AU  - Bush SJ
AD  - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of 
      Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
FAU - Lefevre, Lucas
AU  - Lefevre L
AD  - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of 
      Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
FAU - McCulloch, Mary E B
AU  - McCulloch MEB
AD  - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of 
      Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
FAU - Lisowski, Zofia M
AU  - Lisowski ZM
AD  - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of 
      Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
FAU - Muriuki, Charity
AU  - Muriuki C
AD  - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of 
      Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
FAU - Waddell, Lindsey A
AU  - Waddell LA
AD  - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of 
      Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
FAU - Sauter, Kristin A
AU  - Sauter KA
AD  - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of 
      Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
FAU - Pridans, Clare
AU  - Pridans C
AD  - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of 
      Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
FAU - Clark, Emily L
AU  - Clark EL
AD  - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of 
      Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
FAU - Hume, David A
AU  - Hume DA
AD  - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of 
      Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
AD  - Mater Research-University of Queensland, Translational Research Institute, 
      Woolloongabba, Brisbane, Queensland 4102, Australia.
LA  - eng
GR  - MR/K001744/1/MRC_/Medical Research Council/United Kingdom
GR  - BBS/E/D/20211550/BB_/Biotechnology and Biological Sciences Research 
      Council/United Kingdom
GR  - BB/L001209/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/L004623/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BBS/E/D/20211552/BB_/Biotechnology and Biological Sciences Research 
      Council/United Kingdom
PT  - Journal Article
PL  - United States
TA  - Immunohorizons
JT  - ImmunoHorizons
JID - 101708159
PMC - PMC6245571
MID - EMS80278
COIS- Disclosures The authors have no financial conflicts of interest.
EDAT- 2018/11/24 06:00
MHDA- 2018/11/24 06:01
PMCR- 2018/11/20
CRDT- 2018/11/24 06:00
PHST- 2018/11/24 06:00 [entrez]
PHST- 2018/11/24 06:00 [pubmed]
PHST- 2018/11/24 06:01 [medline]
PHST- 2018/11/20 00:00 [pmc-release]
AID - 10.4049/immunohorizons.1700073 [doi]
PST - ppublish
SO  - Immunohorizons. 2018 Jan 1;2(1):27-37. doi: 10.4049/immunohorizons.1700073.