PMID- 7852845
OWN - NLM
STAT- MEDLINE
DCOM- 19950314
LR  - 20190516
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 57
IP  - 2
DP  - 1995 Feb
TI  - Cyclic GMP and guanylate cyclase mediate lipopolysaccharide-induced Kupffer cell 
      tumor necrosis factor-alpha synthesis.
PG  - 297-302
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an important mediator in sepsis and 
      septic shock. Kupffer cells (KCs) are the resident macrophages of the liver and 
      are potent producers of TNF-alpha in response to inflammatory stimuli such as 
      bacterial endotoxin or lipopolysaccharide (LPS). Although the effects of 
      exogenous cytokines such as interferon-gamma on TNF-alpha production by 
      macrophages have been fairly well studied, the intracellular pathways regulating 
      KC TNF-alpha synthesis are largely unknown. We investigated the role of guanylate 
      cyclase and cGMP in LPS-induced KC TNF-alpha synthesis. Exogenous 8-BrcGMP and 
      dbcGMP increased LPS-stimulated TNF-alpha synthesis but had no effect on KC 
      TNF-alpha in the absence of LPS. Sodium nitroprusside (SNP), a nitric 
      oxide-releasing substance that stimulates guanylate cyclase, increased TNF-alpha 
      synthesis in response to LPS, whereas methylene blue and LY83583, guanylate 
      cyclase inhibitors, decreased KC TNF-alpha synthesis. The inhibitory effect of 
      methylene blue could be overcome with exogenous dbcGMP or SNP. Our results 
      demonstrate that guanylate cyclase and cGMP mediate LPS-induced KC TNF-alpha 
      synthesis and suggest that agents that alter cyclic nucleotide metabolism in KCs 
      may affect the response of these cells to inflammation and inflammatory stimuli.
FAU - Harbrecht, B G
AU  - Harbrecht BG
AD  - Department of Surgery, University of Pittsburgh, Pennsylvania.
FAU - Wang, S C
AU  - Wang SC
FAU - Simmons, R L
AU  - Simmons RL
FAU - Billiar, T R
AU  - Billiar TR
LA  - eng
GR  - GM-37753/GM/NIGMS NIH HHS/United States
GR  - GM-44100/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Aminoquinolines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (SRS-A)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 169D1260KM (Nitroprusside)
RN  - 31356-94-2 (8-bromocyclic GMP)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 32266-35-6 (Dibutyryl Cyclic GMP)
RN  - 91300-60-6 (6-anilino-5,8-quinolinedione)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - H2D2X058MU (Cyclic GMP)
RN  - T42P99266K (Methylene Blue)
SB  - IM
MH  - Aminoquinolines/pharmacology
MH  - Animals
MH  - Cell Membrane Permeability
MH  - Cells, Cultured
MH  - Cyclic GMP/analogs & derivatives/pharmacology/*physiology
MH  - Dibutyryl Cyclic GMP/pharmacology
MH  - Guanylate Cyclase/antagonists & inhibitors/drug effects/*physiology
MH  - Kupffer Cells/drug effects/metabolism/*physiology
MH  - Lipopolysaccharides/*pharmacology
MH  - Male
MH  - Methylene Blue/pharmacology
MH  - Nitric Oxide/metabolism
MH  - Nitroprusside/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - SRS-A/antagonists & inhibitors
MH  - Second Messenger Systems/drug effects/physiology
MH  - Stimulation, Chemical
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
EDAT- 1995/02/01 00:00
MHDA- 1995/02/01 00:01
CRDT- 1995/02/01 00:00
PHST- 1995/02/01 00:00 [pubmed]
PHST- 1995/02/01 00:01 [medline]
PHST- 1995/02/01 00:00 [entrez]
AID - 10.1002/jlb.57.2.297 [doi]
PST - ppublish
SO  - J Leukoc Biol. 1995 Feb;57(2):297-302. doi: 10.1002/jlb.57.2.297.