PMID- 9000533
OWN - NLM
STAT- MEDLINE
DCOM- 19970210
LR  - 20190516
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 61
IP  - 1
DP  - 1997 Jan
TI  - Elevated levels of NO in both unchallenged and LPS-challenged C. parvum-primed 
      mice are attributable to the activity of a cytokine-inducible isoform of iNOS.
PG  - 24-32
AB  - Elevated levels of nitric oxide (NO2-/NO3-) were detected in the serum of mice 
      3-7 days after priming with Corynebacterium parvum (Propionibacterium acnes). The 
      serum NO2-/NO3- response was completely inhibited when C. parvum-primed (C. 
      parrum) mice were treated with N(G)-monomethyl-L-arginine (L-NMMA) or 
      aminoguanidine (AG) on days 6 and 7 post priming. The response was also inhibited 
      when the mice were treated with interleukin-10 (IL-10) and the cytokine was most 
      effective when given in multiple doses beginning on the day of priming. In 
      contrast to L-NMMA and AG, IL-10 had no effect on the serum NO2-/NO3- response 
      when administered to the mice on days 6 and 7 post priming. The inducible isoform 
      of NOS (iNOS) appeared to be responsible for the elevated NO2-/NO3- response in 
      C. parvum mice because iNOS transcripts were readily detected in their livers. 
      Moreover, these transcripts as well as the circulating levels of NO2-/NO3- were 
      dramatically reduced when the mice were treated with anti-tumor necrosis factor 
      alpha (anti-TNF-alpha) or anti-interferon-gamma (anti-IFN-gamma) monoclonal 
      antibodies (mAbs) during the priming interval. There was a modest increase (less 
      than twofold) in the serum NO2-/NO3- response following a lipopolysaccharide 
      (LPS) challenge to C. parvum mice (C. parvum/LPS mice). LPS had a more dramatic 
      stimulatory effect if the levels of NO2-/NO3- preexisting in C. parvum/LPS mice 
      were reduced by treatment with L-NMMA, AG, or IL-10 before the challenge. Thus 
      the levels of NO2-/NO3- that preexisted in C. parvum/LPS mice appeared to 
      influence their ability to mount a NO2-/NO3- response subsequent to the LPS 
      challenge. The NO2-/NO3- response did not contribute to lethality in C. 
      parvum/LPS mice because anti-TNF-alpha and anti-IFN-gamma mAbs were protective 
      but had no effect on serum NO2-/NO3- levels when administered to mice 24 h before 
      the LPS challenge.
FAU - Smith, S R
AU  - Smith SR
AD  - Department of Immunology, Schering-Plough Research Institute, Kenilworth, New 
      Jersey 07033, USA.
FAU - Manfra, D
AU  - Manfra D
FAU - Davies, L
AU  - Davies L
FAU - Terminelli, C
AU  - Terminelli C
FAU - Denhardt, G
AU  - Denhardt G
FAU - Donkin, J
AU  - Donkin J
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Guanidines)
RN  - 0 (Isoenzymes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 27JT06E6GR (omega-N-Methylarginine)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - SCQ4EZQ113 (pimagedine)
SB  - IM
MH  - Animals
MH  - Guanidines/pharmacology
MH  - Interferon-gamma/antagonists & inhibitors/blood/*physiology
MH  - Interleukin-10/pharmacology
MH  - Isoenzymes/antagonists & inhibitors/*biosynthesis
MH  - Lipopolysaccharides/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Nitrates/*blood
MH  - Nitric Oxide Synthase/antagonists & inhibitors/*biosynthesis
MH  - Nitrites/*blood
MH  - *Propionibacterium acnes
MH  - Recombinant Proteins/pharmacology
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/analysis/antagonists & inhibitors/*physiology
MH  - omega-N-Methylarginine/pharmacology
EDAT- 1997/01/01 00:00
MHDA- 1997/01/01 00:01
CRDT- 1997/01/01 00:00
PHST- 1997/01/01 00:00 [pubmed]
PHST- 1997/01/01 00:01 [medline]
PHST- 1997/01/01 00:00 [entrez]
AID - 10.1002/jlb.61.1.24 [doi]
PST - ppublish
SO  - J Leukoc Biol. 1997 Jan;61(1):24-32. doi: 10.1002/jlb.61.1.24.