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MY4 at 10 ug/mL diminished coriariin A's ability to induce TNFα
secretion compared to control by about 70%, whereas the
gallotannin/ellagitannin analogue 81 was a little better at competing with
MY4 (approximately 55% reduction in TNFα formation). These results
clearly demand a role for CD14 in the tannin-mediated induction of
TNFα secretion from hPBMC's, but the data are not as convincing as
with the natural ligand LPS. The intervention of other, non-CD14-
utilizing pathways may be indicated for the tannins, perhaps involving
the selectin receptors discussed along with Fig. 6.4. Nevertheless, the
evidence is unequivocal that at least some of the TNFα-generating
pathway stimulated by tannins follows the same receptor system as does
the natural ligand LPS/lipid A.
4000
3500
3000
2500
TNF α
(pg/mL)
2000
1500
1000
500
0
LPS (2.5
ng/mL)
LPS/MY4
dimer 82
(27uM)
dimer
82/MY4
coriariin A
62 (27 uM)
coriariin A
62/MY4
Fig. 6.18 The monoclonal antibody to CD14 suppresses TNFα release from hPBMC's
stimulated by (a) LPS, (b) the model dimer 81 , and (c) coriariin A ( 62 ).
6.4.2 Use of HeJ/OuJ mice as a probe for TLR-4 participation in
tannin-stimulated TNF α release
A strain of otherwise healthy mice that was nonresponsive to LPS
stimulation were discovered in the 1960s (Nutini et al. , 1963, Hoshino
et al. , 1999). Subsequent studies traced this condition to a mutation in the
TLR4 gene, which rendered the receptor inactive. This difference in
 
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