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COL-3, a chemically modified tetracycline, inhibits lipopolysaccharide-induced microglia activation and cytokine expression in the brain.

Edan RA, Luqmani YA, Masocha W - PLoS ONE (2013)

Bottom Line: Tetracycline antibiotics such as minocycline inhibit microglial activation and cytokine expression during CNS inflammation.COL-3 has been described to have no antibacterial activity.Our data show that COL-3 has some antibacterial activity against S. aureus, inhibits LPS-induced neuroinflammation, and displays potential as a therapeutic agent for treatment of conditions involving CNS inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, Safat, Kuwait.

ABSTRACT
Microglia activation results in release of proinflammatory molecules including cytokines, which contribute to neuronal damage in the central nervous system (CNS) if not controlled. Tetracycline antibiotics such as minocycline inhibit microglial activation and cytokine expression during CNS inflammation. In the present study we found that administration of chemically modified tetracycline-3 (COL-3), inhibits lipopolysaccharide (LPS)-induced microglial and p38 MAPK activation, as well as the increase in TNF-α, but not IL-1β expression, in the brains of BALB/c mice. COL-3 has been described to have no antibacterial activity. We observed that COL-3 had no activity against a Gram-negative bacteria, Escherichia coli; however surprisingly, COL-3 had antibacterial activity against a Gram-positive bacteria Staphylococcus aureus, with a minimum inhibitory concentration of 1 mg/ml. Our data show that COL-3 has some antibacterial activity against S. aureus, inhibits LPS-induced neuroinflammation, and displays potential as a therapeutic agent for treatment of conditions involving CNS inflammation.

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Effects of COL-3 on LPS-induced up-regulation of cytokine transcript levels in the brain.Relative expression of IL-1β and TNF-α mRNA in brains of control mice, LPS-inoculated vehicle-treated and LPS-inoculated COL-3-treated mice at 24 h post LPS inoculation. Each bar represents the mean ± S.E.M of the values obtained from 4 (for TNF-α) –12 (for IL-1β) animals. *P<0.05 compared to control animals and #P<0.05 compared to LPS-inoculated mice pretreated with vehicle.
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pone-0057827-g004: Effects of COL-3 on LPS-induced up-regulation of cytokine transcript levels in the brain.Relative expression of IL-1β and TNF-α mRNA in brains of control mice, LPS-inoculated vehicle-treated and LPS-inoculated COL-3-treated mice at 24 h post LPS inoculation. Each bar represents the mean ± S.E.M of the values obtained from 4 (for TNF-α) –12 (for IL-1β) animals. *P<0.05 compared to control animals and #P<0.05 compared to LPS-inoculated mice pretreated with vehicle.

Mentions: The levels of the cytokines IL-1β and TNF-α mRNA were increased in the brains of LPS-inoculated mice compared to vehicle-injected controls. Treatment with COL-3 significantly reduced LPS-induced TNF-α, but not IL-1β mRNA expression (Fig. 4).


COL-3, a chemically modified tetracycline, inhibits lipopolysaccharide-induced microglia activation and cytokine expression in the brain.

Edan RA, Luqmani YA, Masocha W - PLoS ONE (2013)

Effects of COL-3 on LPS-induced up-regulation of cytokine transcript levels in the brain.Relative expression of IL-1β and TNF-α mRNA in brains of control mice, LPS-inoculated vehicle-treated and LPS-inoculated COL-3-treated mice at 24 h post LPS inoculation. Each bar represents the mean ± S.E.M of the values obtained from 4 (for TNF-α) –12 (for IL-1β) animals. *P<0.05 compared to control animals and #P<0.05 compared to LPS-inoculated mice pretreated with vehicle.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585197&req=5

pone-0057827-g004: Effects of COL-3 on LPS-induced up-regulation of cytokine transcript levels in the brain.Relative expression of IL-1β and TNF-α mRNA in brains of control mice, LPS-inoculated vehicle-treated and LPS-inoculated COL-3-treated mice at 24 h post LPS inoculation. Each bar represents the mean ± S.E.M of the values obtained from 4 (for TNF-α) –12 (for IL-1β) animals. *P<0.05 compared to control animals and #P<0.05 compared to LPS-inoculated mice pretreated with vehicle.
Mentions: The levels of the cytokines IL-1β and TNF-α mRNA were increased in the brains of LPS-inoculated mice compared to vehicle-injected controls. Treatment with COL-3 significantly reduced LPS-induced TNF-α, but not IL-1β mRNA expression (Fig. 4).

Bottom Line: Tetracycline antibiotics such as minocycline inhibit microglial activation and cytokine expression during CNS inflammation.COL-3 has been described to have no antibacterial activity.Our data show that COL-3 has some antibacterial activity against S. aureus, inhibits LPS-induced neuroinflammation, and displays potential as a therapeutic agent for treatment of conditions involving CNS inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, Safat, Kuwait.

ABSTRACT
Microglia activation results in release of proinflammatory molecules including cytokines, which contribute to neuronal damage in the central nervous system (CNS) if not controlled. Tetracycline antibiotics such as minocycline inhibit microglial activation and cytokine expression during CNS inflammation. In the present study we found that administration of chemically modified tetracycline-3 (COL-3), inhibits lipopolysaccharide (LPS)-induced microglial and p38 MAPK activation, as well as the increase in TNF-α, but not IL-1β expression, in the brains of BALB/c mice. COL-3 has been described to have no antibacterial activity. We observed that COL-3 had no activity against a Gram-negative bacteria, Escherichia coli; however surprisingly, COL-3 had antibacterial activity against a Gram-positive bacteria Staphylococcus aureus, with a minimum inhibitory concentration of 1 mg/ml. Our data show that COL-3 has some antibacterial activity against S. aureus, inhibits LPS-induced neuroinflammation, and displays potential as a therapeutic agent for treatment of conditions involving CNS inflammation.

Show MeSH
Related in: MedlinePlus