Signal transduction underlying stroke-induced gliosis and in-Beta ammation as therapeutic target

• Autorzy: Kaminska B.
• Języki publikacji: EN

Abstrakty

EN

Excessive, uncontrolled infl ammation and gliosis contribute to a majority of neurologic disorders despite of their different etiology. Activated microglial cells release pro-infl ammatory cytokines, infl ammation mediators, matrix proteinases and toxic factors. Reactive astrogliosis involves astrocyte proliferation, activation and hypertrophy accompanied by production of cytokines, growth factors and metabolic alterations. Infl ammatory signalling involves activation of transcription factors NFκB and MAP kinases as critical signal transducers. We demonstrate activation of JAK/STAT (signal transducers and activators of transcription) signaling pathway associated with infl ammatory microglia and ìreactive astrogliosisî in vitro when primary rat astrocyte cultures were stimulated with the pro-infl ammatory cytokines (IL1-β, IFN-γ and TNF-α). Global gene expression profi ling revealed a coordinated and strong upregulation of infl ammatory and immune response genes in infl ammatory microglia in vitro and after transient focal ischemia. Moreover, we found a large representation of STAT responsive genes in both conditions suggesting a strong contribution of STAT pathway to stroke-induced infl ammation. We studied whether inhibition of signal transduction mediated by MAP kinases and JAK/STAT pathway interferes with expression/release of infl ammatory cytokines, mediators, matrix proteinases and toxic factors by activated glial cells. Our fi ndings establish immunosuppressants as effective therapeutic candidate for use in the treatment of human neurologic disorders. Identifi cation of STAT dependent events underlying infl ammation and development specifi c inhibitors may facilitate development of innovative strategies blocking hostile microglial responses to control infl ammation.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.93

Twórcy

autor

Kaminska B.

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