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.