Cytokine release and inhibiting effect of ENV59-GP3 and of
NS6180 in stimulated THP-1 cells
The ENV59-GP3 peptide inhibits the production of pro-inflammatory
cytokines in activated THP-1 cells [9]. To elucidate whether
KCa3.1 plays any role in this phenotypic activity of
ENV59-GP3 peptide, expression and activity of the KCa3.1
channels in THP-1 cells were confirmed by qPCR (Figure 3B). Patch clamp
experiments confirmed existence of currents sensitive to specific
KCa3.1 channel blocker (NS6180) and channel opener
(NS309, Figure 3A). Next we studied if the inhibitory effect of
ENV59-GP3 in cytokine production mimics that of NS6180, a potent and
highly selective small molecule inhibitor of KCa3.1
channels [18]. Our results (Figure 3C) corroborate the notion that
KCa3.1 is an important regulator of synthesis and
release of proinflammatory cytokines in THP-1 cells and that the
ENV59-GP3 peptide and the channel blocker NS6180 have similar effects on
cytokine production in these cells.