PMID- 12028827
OWN - NLM
STAT- MEDLINE
DCOM- 20020613
LR  - 20131121
IS  - 1528-7394 (Print)
IS  - 0098-4108 (Linking)
VI  - 65
IP  - 10
DP  - 2002 May 24
TI  - Role of mitogen-activated protein kinase activation in the production of 
      inflammatory mediators: differences between primary rat alveolar macrophages and 
      macrophage cell lines.
PG  - 757-68
AB  - Stimulation of macrophages has been shown to activate all three families of 
      mitogen activated protein kinases (MAPKs). However, variable results are reported 
      in the literature with respect to the particular kinases activated with any given 
      stimulus. In this study, the role of activation of MAPKs was examined in the 
      production of inflammatory mediators by measuring the phosphorylation of the 
      kinases and their ability to phosphorylate specific substrates in rat primary 
      alveolar macrophages, a rat alveolar macrophage cell line (NR8383), and two mouse 
      monocytic cell lines (RAW 264.7 and J774A.1). In the three cell lines examined, 
      all three families of MAPKs were activated upon stimulation with either 
      lipopolysaccharide (LPS) or LPS plus interferon-gamma; in contrast, only ERK1/2 
      was activated in primary rat alveolar macrophages upon stimulation with LPS. 
      Inhibition of ERK1/2 activation by the MEK inhibitor PD98059 abrogated nitric 
      oxide and tumor necrosis factor-alpha (TNF-alpha) production in primary rat 
      alveolar macrophages, but the p38 inhibitor SB203580 had no effect on the 
      production of these two inflammatory mediators. These observations indicate that 
      MAPK activation is cell specific and explain some of the conflicting results 
      reported in the literature. These studies emphasize the need to exercise caution 
      in extrapolating data from cell lines to primary cells.
FAU - Rao, K Murali Krishna
AU  - Rao KM
AD  - Pathology and Physiology Research Branch, Health Effects Laboratory Division, 
      National Institute for Occupational Safety and Health, Morgantown, West Virginia 
      26505, USA. mir8@cdc.gov
FAU - Meighan, Terence
AU  - Meighan T
FAU - Bowman, Linda
AU  - Bowman L
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Toxicol Environ Health A
JT  - Journal of toxicology and environmental health. Part A
JID - 100960995
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line/immunology
MH  - Enzyme Activation/immunology
MH  - Interferon-gamma/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - MAP Kinase Signaling System
MH  - Macrophages, Alveolar/*immunology
MH  - Male
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/immunology/*metabolism
MH  - Monocytes/*immunology
MH  - Nitric Oxide/analysis
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Specific Pathogen-Free Organisms
MH  - Substrate Specificity
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2002/05/25 10:00
MHDA- 2002/06/14 10:01
CRDT- 2002/05/25 10:00
PHST- 2002/05/25 10:00 [pubmed]
PHST- 2002/06/14 10:01 [medline]
PHST- 2002/05/25 10:00 [entrez]
AID - 10.1080/00984100290071027 [doi]
PST - ppublish
SO  - J Toxicol Environ Health A. 2002 May 24;65(10):757-68. doi: 
      10.1080/00984100290071027.