A suplementação de vitamina C inibe hiperativação de células de Leucemia Mielóide Crônica induzidas por Lipopolysaccarídeo: envolvimento da sinalização purinérgica

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, characterized by overproduction of white blood cells, with the patients presenting anemia, fatigue, infections, bleeding, and other problems. Thus, an important goal for CML patients is to prevent infections and inhibit the exacerbation of inflammatory processes. In this context, the present study investigated whether vitamin C could inhibit hyperinflammatory activation of K562 cells induced by LPS and whether purinergic signaling is involved in such response. Two doses of vitamin C were used (5 µg/mL and 10 µg/mL) for 2 hours prior LPS (10ng/mL) for 22 hours in K-562 cells (3x105 cells/mL/well). The results demonstrated that both doses of vitamin C significantly reduced LPS-induced the release of IL-6 (5 µg/mL, p<0.01 and 10µg/mL p<0.01) and TNF-alpha (5 µg/mL, p<0.01 and 10µg/mL p<0.01). In contrast, both doses of vitamin C induced the release of the anti-inflammatory cytokine IL-10 (5 µg/mL, p<0.01 and 10µg/mL p<0.01). In addition, 10µg/mL of vitamin C induced the release of klotho(10µg/mL p<0.01), an anti-aging and antiinflammatory protein. Importantly, vitamin C (5 µg/mL, p<0.01 and 10µg/mL p<0.01) reduced ATP release and accumulation in the extracellular milieu as well as reduce the expression at mRNA levels of P2X7 receptor, suggesting a possible mechanism of action. Therefore, we conclude that vitamin C inhibits hyperinflammatory state induced by LPS in K-562 cells involving purinergic signaling.