COL-3 performs as a potent anti-inflammatory drug for LPS- and
αSa-activated microglial cells
Our group has previously demonstrated, in newborn mice primary
microglial cultures, the robust inflammatory action of LPS and αSa as
these inflammogens stimulated the production/release of the
proinflammatory cytokine TNF-α and glutamate, a non-cytokine
inflammatory mediator [30,32,35]. The present study pointedly
demonstrates that COL-3, when administered at 10 and 20 μM restrained or
almost entirely abolished the release of TNF-α and Iba-1 expression
induced by LPS or αSa in microglial cell cultures, an absent effect at 1
μM, indicating that COL-3 presents a threshold concentration.
Previous studies sustain our findings, as COL-3 can restrain the
development of paclitaxel-induced thermal hyperalgesia, effect
associated to a COL-3 protection against CD11b+ cells increase – a
surface protein expressed by many immune cells, such as macrophage and
microglial cells – and cytokine production, such as TNF-α and Il-1β
[41]. In the study of Cazalis et al. (2009) [42], using anex vivo human whole blood model, it was shown that LPS increased
cytokines’ secretion, and COL-3 reduced LPS-induced cytokine secretion
at several degrees. This outcome was centrally reproduced in an in
vivo model of inflammation, where COL-3 was able to prevent, at least
partially, microglia activation and TNF-α (but not IL-1β) release in the
brain [26]. Our results suggest the efficacy of COL-3 is more
effective than the reference tetracycline DOX in restraining
inflammation produced by LPS or αSa, since the effect of COL-3 lower
concentrations (10 and 20 µM) toward TNF-α and Iba-1 expression was
sufficient to mimic the effect of a higher DOX concentration (50 µM) or
of the classic glucocorticoid anti-inflammatory, DEX.