TY - JOUR
T1 - Nuclear Factor-κB Blockade Attenuates but Does Not Abrogate Lipopolysaccharide-Dependent Tumor Necrosis Factor-α Biosynthesis in Alveolar Epithelial Cells
AU - Haddad, John J.
AU - Land, Stephen C.
PY - 2001/7/13
Y1 - 2001/7/13
N2 - We have investigated the role that the nuclear factor (NF)-κB plays in regulating the biosynthesis of tumor necrosis factor (TNF)-α, an inflammatory cytokine. Irreversible inhibition of the proteasome complex by carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG-132; 1-50 μM) had no inhibitory effect on LPS-mediated TNF-α biosynthesis. Furthermore, selective inhibition of NF-κB by the action of caffeic acid phenylethyl ester (CAPE; 1-100 μM) and sulfasalazine (SSA; 0.1-10 μM), a potent and irreversible inhibitor of NF-κB, partially attenuated, but did not abolish, LPS-dependent TNF-α secretion. Incorporation of a selectively permeant inhibitor of NF-®B, SN-50 (1-20 μM), a peptide which contains the nuclear localization sequence (NLS) for the p50 NF-κB subunit, and the amino-terminal sequence of Kaposi fibroblast growth factor to promote cell permeability, attenuated in a dose-dependent manner LPS-mediated release of TNF-α It is concluded that the NF-κB pathway is partially implicated and that its blockade attenuates, but does not abrogate, LPS-dependent TNF-α biosynthesis in alveolar epithelial cells.
AB - We have investigated the role that the nuclear factor (NF)-κB plays in regulating the biosynthesis of tumor necrosis factor (TNF)-α, an inflammatory cytokine. Irreversible inhibition of the proteasome complex by carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG-132; 1-50 μM) had no inhibitory effect on LPS-mediated TNF-α biosynthesis. Furthermore, selective inhibition of NF-κB by the action of caffeic acid phenylethyl ester (CAPE; 1-100 μM) and sulfasalazine (SSA; 0.1-10 μM), a potent and irreversible inhibitor of NF-κB, partially attenuated, but did not abolish, LPS-dependent TNF-α secretion. Incorporation of a selectively permeant inhibitor of NF-®B, SN-50 (1-20 μM), a peptide which contains the nuclear localization sequence (NLS) for the p50 NF-κB subunit, and the amino-terminal sequence of Kaposi fibroblast growth factor to promote cell permeability, attenuated in a dose-dependent manner LPS-mediated release of TNF-α It is concluded that the NF-κB pathway is partially implicated and that its blockade attenuates, but does not abrogate, LPS-dependent TNF-α biosynthesis in alveolar epithelial cells.
KW - Inflammation
KW - Lipopolysaccharide
KW - NF-κB
KW - Proteasome
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=0034741277&partnerID=8YFLogxK
U2 - 10.1006/bbrc.2001.5172
DO - 10.1006/bbrc.2001.5172
M3 - Article
C2 - 11444836
AN - SCOPUS:0034741277
VL - 285
SP - 267
EP - 272
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -