Heligmosomoides polygyrus antigens variably activated NF-κB

of MLN cells of uninfected and infected mice. The growing activity of p50 was observed after infection, and additionally, complete antigen and F9 enhanced p50 activity in the cytoplasm and nucleus; p50 as a homodimer is a repressor of κB site transcription in the cytoplasm [41], but it also participates in target gene transactivation by forming heterodimers with p65 [42]. In our studies, the level of NF-κB subunits, for example, p50 and p65 both in the cytoplasm and nuclei were distinct, and elevated activity of p50 was observed both in the cytoplasm and nuclei. After infection and after restimulation with H. polygyrus antigen fractions, expression AZD9291 manufacturer of p65 in cytoplasm rather decreased. As heterodimer p50/p65 translocated, increasing

activity of p50 was observed in nucleus both after infection and also when cells were treated with the nematode antigens. F9 like F17 up-regulated p50 and F17 strongly reduced activation of p65 in nucleus. Activation of NF-κB is essential for both cell proliferation and resistance of cells to apoptosis [43]. Infection with filarial parasites transitorily activated the factor with degradation of the cytoplasmic inhibitor protein IκΒ, and ES-62, a molecule secreted by filarial nematodes selectively blocks signal transduction events including NF-κB activation [44, 45]. The mechanism by which the parasite triggers and regulates activation of NF-κB is unspecified [46] and more detailed studies with recognition of receptor pathway induction with separate molecules Ku0059436 of H. polygyrus antigens might be promising. Selectively enhanced p50 activity and antiapoptotic activity of antigen fractions support an observation that cells might be hyporesponsive. DEX-induced apoptosis also requires protein synthesis

[47]. Heligmosomoides polygyrus-originated factors may inhibit apoptosis inducing enzymatic pathway, which depends on glucocorticoid Avelestat (AZD9668) receptor or that regulates the activity of NF-κB [48] and are potent to restore activation of protein kinase pathways and support survival of the cells. Our study identified H. polygyrus antigen factors with potential activity for regulation of surviving T-cell populations. These fractions can simultaneously target c-FLIP, Bcl-2 expression and increase p50 activity in mice infected with the parasite. Heligmosomoides polygyrus antigens contain many different proteins, which may have distinct activity in apoptosis. The content of protein fractions was compared with H. polygyrus-secreted proteins [13]. As we used somatic homogenate of adult stages, identified proteins were representative for cytoskeleton and metabolic pathways. There were also proteins which are specific for each fraction. The differences between F9, F13 and F17 fractions are their distinct antiapoptotic activity to different cell populations and also with distinct activation of NF-κB subunits.