Giardia intestinalis is a protozoan that causes a generally self-limited clinical illness typically characterized by diarrhea, abdominal cramps, bloating, weight loss and malabsorption. The pathogenesis of giardiasis is multifactorial and probably different in various animal models, but the mechanisms responsible for the disease are still poorly understood. We previously reported that G. intestinalis is able to induce apoptosis in the human HCT-8 epithelial cell line through the activation of both the intrinsic and extrinsic apoptotic pathways. In the present study we demonstrate that activation of the mitogen-activated protein kinases (MAPKs) plays an important role in the regulation of HCT-8 cell apoptosis induced by G. intestinalis. MAPK activation seems to correlate with regulation of the apoptotic process because specific MAPK inhibitors significantly reduced the expression of the active form of caspase-3 in infected cells. Apoptotic changes were also dramatically inhibited by pre-treatment of the cells with JNK or p38 specific inhibitors, but not ERK 1/2 inhibitor. Taken together, these results suggest a critical role for MAPK activation in G. intestinalis-induced apoptosis in the human HCT-8 cell line.
MAP Kinases are Required for Apoptosis of HCT-8 Epithelial Cells Induced by the Parasite Giardia intestinalis
PANARO, Maria Antonietta;CIANCIULLI, ANTONIA;CALVELLO, Rosa;
2012-01-01
Abstract
Giardia intestinalis is a protozoan that causes a generally self-limited clinical illness typically characterized by diarrhea, abdominal cramps, bloating, weight loss and malabsorption. The pathogenesis of giardiasis is multifactorial and probably different in various animal models, but the mechanisms responsible for the disease are still poorly understood. We previously reported that G. intestinalis is able to induce apoptosis in the human HCT-8 epithelial cell line through the activation of both the intrinsic and extrinsic apoptotic pathways. In the present study we demonstrate that activation of the mitogen-activated protein kinases (MAPKs) plays an important role in the regulation of HCT-8 cell apoptosis induced by G. intestinalis. MAPK activation seems to correlate with regulation of the apoptotic process because specific MAPK inhibitors significantly reduced the expression of the active form of caspase-3 in infected cells. Apoptotic changes were also dramatically inhibited by pre-treatment of the cells with JNK or p38 specific inhibitors, but not ERK 1/2 inhibitor. Taken together, these results suggest a critical role for MAPK activation in G. intestinalis-induced apoptosis in the human HCT-8 cell line.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
