MAP Kinases are Required for Apoptosis of HCT-8 Epithelial Cells Induced by the Parasite Giardia intestinalis

Giardia intestinalis is a protozoan that causes a generally self-limited clinical illness typically characterized by\uddiarrhea, abdominal cramps, bloating, weight loss and malabsorption. The pathogenesis of giardiasis is multifactorial\udand probably different in various animal models, but the mechanisms responsible for the disease are still poorly\udunderstood. We previously reported that G. intestinalis is able to induce apoptosis in the human HCT-8 epithelial cell\udline through the activation of both the intrinsic and extrinsic apoptotic pathways. In the present study we demonstrate\udthat activation of the mitogen-activated protein kinases (MAPKs) plays an important role in the regulation of HCT-8\udcell apoptosis induced by G. intestinalis. MAPK activation seems to correlate with regulation of the apoptotic process\udbecause specific MAPK inhibitors significantly reduced the expression of the active form of caspase-3 in infected\udcells. Apoptotic changes were also dramatically inhibited by pre-treatment of the cells with JNK or p38 specific\udinhibitors, but not ERK 1/2 inhibitor. Taken together, these results suggest a critical role for MAPK activation in G.\udintestinalis-induced apoptosis in the human HCT-8 cell line