Inhibition of infiltration and activation of brain macrophages underlies antitumor activity of systemically administered cyclosporin A.

• Autorzy: Gabrusiewicz K. , Ellert-Miklaszewska A. , Sielska M. , Frankowska M. , Kaminska B.
• Języki publikacji: EN

Abstrakty

EN

Malignant glioblastomas are characterized by infi ltration of tumour tissue with brain macrophages that contribute to tumour progression through release a variety of growth factors, cytokines/ chemokines supporting tumor growth, invasion and the immune system evasion. Thus targeting of cytokine production, infi ltration and activation of macrophages may be a novel antitumor strategy. In the present study, we investigated an effectiveness and molecular mechanisms mediating antitumor effects of CsA in the murine glioma model. EGFP-GL261 glioma cells were injected into the striatum of C57BL/6 mice and tumor-bearing mice received CsA (2 or 10 mg/kg/i.p.) every 2 days from 2nd or 8th day after implantation. CsA-treated mice had signifi cantly smaller tumors than control mice. When the treatment was postponed to 8th day, only the higher dose of CsA was effective. CsA-treated mice showed a diminished number of tumor-infi ltrating, amoeboid brain macrophages. TUNEL staining revealed a DNA fragmentation mostly within infi ltrating macrophages after CsA treatment. At concentrations <10 μM CsA did not affect proliferation or viability of cultured glioma cells. Elevated IL-10 and GM-CSF levels were found in tumor-bearing hemisphere in comparison to naive controls and CsA treatment reduced signifi cantly cytokine levels. Our fi ndings demonstrate that CsA-induced decrease of cytokine production, infi ltration and activation of macrophages results in reduction of glioma growth and progression.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.346

Twórcy

autor

Gabrusiewicz K.

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

autor

Ellert-Miklaszewska A.

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

autor

Sielska M.

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

autor

Frankowska M.

• 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