FK506 prevents pro-inß ammatory and cytotoxic activation of cytokine-stimulated rat astrocytes

• Autorzy: Gozdz A. , Kaminska B.
• Języki publikacji: EN

Abstrakty

EN

Reactive astrogliosis is implicated in many acute and chronic neuropathological conditions and involves astrocyte proliferation, activation and hypertrophy accompanied by production of cytokines, growth factors and metabolic alterations. Astrocyte activation may exert both benefi cial and detrimental effects on nervous system cells, therefore its modulation is an attractive target for neuroprotective therapies. We have demonstrated that a widely used immunosuppressant and calcineurin inhibitior FK506 potently reduced gliosis in vivo and improved recovery in a rat stroke model (Zawadzka and Kaminska 2004, Glia 49: 36ñ51). To dissect the mechanism of FK506 action on activated astrocytes, we employed a model of ìreactive astrogliosis in vitroî based on primary rat astrocyte cultures stimulated with the mixture of pro-infl ammatory cytokines: IL1-beta, IFN-gamma and TNF-alpha. Cytokine cocktail induced activation of NFkappaB, p38 MAPK and JNK signaling pathways followed by cellular hypertrophy, rearrangement of astrocyte cytoskeleton, nitric oxide production and expression of mRNA for IL-6 and trail. FK506, as well as another calcineurin inhibitor cyclosporin A, reduced the astrocyte hypertrophy. FK506 decreased the level of activated p38 MAPK, as well as down-regulated trail mRNA. Interestingly, FK506 was also able to reduce the activation of p38 MAPK in astrocytes exposed to hydrogen peroxide implicating potential of this drug in counteracting some effects of oxidative stress observed during ischemic reperfusion or neuroinfl ammation. Our data suggest that FK506 may exert its neuroprotective effect partially via inhibition of the pro-infl ammatory astroglia activation and implicate a calcineurin as a new candidate for triggering of astrogliosis. Supported by PBZ/MEiN/01/2006/32 (AG)

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.97-98

Twórcy

autor

Gozdz A.

• Department of Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Kaminska B.

• Department of Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland