PMID- 9519810
OWN - NLM
STAT- MEDLINE
DCOM- 19980402
LR  - 20190701
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 62
IP  - 12
DP  - 1998
TI  - Protease inhibitors protect macrophages from lipopolysaccharide-induced 
      cytotoxicity: possible role for NF-kappaB.
PG  - 1081-8
AB  - Recent studies suggest lipopolysaccharide (LPS) mediated cell death as underlying 
      mechanism of hyporesponsiveness and dysfunction of macrophages in the late phase 
      of septic shock. In the present study LPS (0.001 - 30 microg/ml) caused a 
      concentration-dependent toxicity in the macrophage cell line (J774.1A) within 24 
      h. The toxicity induced by LPS (1 microg/ml) was completely inhibited by the 
      serine protease inhibitors, N-alpha-tosyl-L-phenylalanine chloromethyl ketone 
      (TPCK) and N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK) as measured by the 
      mitochondrial-dependent oxidation of 
      3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromid (MTT) to formazan. 
      These inhibitors antagonize the activation of nuclear transcription factor-kappaB 
      (NF-kappaB) indirectly by inhibiting I kappaB alpha-protease. SN50, a direct 
      inhibitor of NF-kappaB translocation into the nucleus also protected macrophages 
      from LPS-mediated toxicity. We conclude from these data that the early phase 
      signal transduction pathway leading to LPS-mediated cytotoxicity in macrophages 
      involves the activation of NF-kappaB. Thus, I kappaB alpha-protease inhibitors 
      might serve as therapeutical agents to maintain macrophage viability during 
      sepsis and to prevent sepsis-induced immune dysfunction.
FAU - Abate, A
AU  - Abate A
AD  - Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther 
      University, Halle (Saale), Germany. abate@pharmazie.uni-halle.de
FAU - Schroder, H
AU  - Schroder H
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Peptides)
RN  - 0 (SN50 peptide)
RN  - 0 (Serine Proteinase Inhibitors)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 2104-86-1 (Tosyllysine Chloromethyl Ketone)
RN  - 402-71-1 (Tosylphenylalanyl Chloromethyl Ketone)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Death/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/metabolism
MH  - Drug Interactions
MH  - *I-kappa B Proteins
MH  - Lipopolysaccharides/*toxicity
MH  - Macrophage Activation/drug effects/physiology
MH  - Macrophages/cytology/*drug effects/physiology
MH  - Mice
MH  - Molecular Sequence Data
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/antagonists & inhibitors/*physiology
MH  - Peptides/metabolism
MH  - Serine Proteinase Inhibitors/*pharmacology
MH  - Signal Transduction/drug effects/physiology
MH  - Tosyllysine Chloromethyl Ketone/*pharmacology
MH  - Tosylphenylalanyl Chloromethyl Ketone/*pharmacology
EDAT- 1998/03/31 00:00
MHDA- 1998/03/31 00:01
CRDT- 1998/03/31 00:00
PHST- 1998/03/31 00:00 [pubmed]
PHST- 1998/03/31 00:01 [medline]
PHST- 1998/03/31 00:00 [entrez]
AID - S0024320598000319 [pii]
AID - 10.1016/s0024-3205(98)00031-9 [doi]
PST - ppublish
SO  - Life Sci. 1998;62(12):1081-8. doi: 10.1016/s0024-3205(98)00031-9.