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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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Related in: MedlinePlus

Effects of COL-3 on LPS-induced p38 MAPK activation in the brain.Confocal laser microscopy images showing immunoreactivity of p38 MAPK in the anterior commissure of fresh frozen sections of mice brains treated with vehicle (MC) (A), LPS (B) and LPS+40 mg/kg COL-3 (C) at 24 h post inoculation. Immunoreactivity of p38 MAPK was increased in LPS inoculated mice (B) compared to control mice (A) and was reduced by treatment with COL-3 (C). Scale bar: 20 µm.
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pone-0057827-g002: Effects of COL-3 on LPS-induced p38 MAPK activation in the brain.Confocal laser microscopy images showing immunoreactivity of p38 MAPK in the anterior commissure of fresh frozen sections of mice brains treated with vehicle (MC) (A), LPS (B) and LPS+40 mg/kg COL-3 (C) at 24 h post inoculation. Immunoreactivity of p38 MAPK was increased in LPS inoculated mice (B) compared to control mice (A) and was reduced by treatment with COL-3 (C). Scale bar: 20 µm.

Mentions: LPS-inoculated animals showed high reactivity of p38 MAPK compared to vehicle-injected controls. Treatment with COL-3 reduced the LPS-induced increase in p38 MAPK immunoreactivity (Fig. 2). Double immunoflourescence showed co-localization of CD11b and p38 MAPK staining in LPS treated animals, indicating up-regulation of p38 MAPK within microglial cells (Fig. 3).


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 p38 MAPK activation in the brain.Confocal laser microscopy images showing immunoreactivity of p38 MAPK in the anterior commissure of fresh frozen sections of mice brains treated with vehicle (MC) (A), LPS (B) and LPS+40 mg/kg COL-3 (C) at 24 h post inoculation. Immunoreactivity of p38 MAPK was increased in LPS inoculated mice (B) compared to control mice (A) and was reduced by treatment with COL-3 (C). Scale bar: 20 µm.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0057827-g002: Effects of COL-3 on LPS-induced p38 MAPK activation in the brain.Confocal laser microscopy images showing immunoreactivity of p38 MAPK in the anterior commissure of fresh frozen sections of mice brains treated with vehicle (MC) (A), LPS (B) and LPS+40 mg/kg COL-3 (C) at 24 h post inoculation. Immunoreactivity of p38 MAPK was increased in LPS inoculated mice (B) compared to control mice (A) and was reduced by treatment with COL-3 (C). Scale bar: 20 µm.
Mentions: LPS-inoculated animals showed high reactivity of p38 MAPK compared to vehicle-injected controls. Treatment with COL-3 reduced the LPS-induced increase in p38 MAPK immunoreactivity (Fig. 2). Double immunoflourescence showed co-localization of CD11b and p38 MAPK staining in LPS treated animals, indicating up-regulation of p38 MAPK within microglial cells (Fig. 3).

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