Likewise, female vs. male patients experienced lower HRQoL, indicating fatigue

jejuni wild type strain, ciaD mutant, and ciaD complemented ABT-888 PARP 阻害剤 isolate bound to INT 407 cells with equal efficiency, as judged by a cell binding assay, Moreover, no difference was observed in the binding of all of the isolates to the host cells over an eight hour period, In separate assays, we found that the inoculation of INT 407 cells with an isolate that contained a knockout in Cj0789, which is the gene immediately downstream of ciaD, resulted in a similar level of secreted IL 8 as that of the wild type strain, Consistent with the pro posal that the delivery of CiaD to host cells requires bacteria host cell contact, the addition of supernatants containing the Cia proteins to INT 407 cells did not induce IL 8 secretion, Based on these data, we concluded that CiaD is an effector protein that is involved in the induction of IL 8 secretion.

CiaD is required for cell invasion We performed experiments to determine if there is a possible link between IL 8 induction and C. jejuni invasion of host cells. The ability of the C. jejuni ciaD mutant to invade INT 407 cells was determined using the gentamicin protection assay. The C. jejuni ciaC mutant was Afatinib 439081-18-2 included as a control, as this mutant displays a significant reduction in cell invasion compared to a wild type strain of C. jejuni. Both the C. jejuni ciaD and ciaC mutants exhibited a reduction in cell invasion when compared to a wild type strain, To determine if cell invasion is required to induce IL 8 secretion from a host cell, INT 407 cells were inoculated with the C. jejuni ciaD and ciaC mutants and the amount of IL 8 secreted into the supernatants was determined.

Consistent with our previous findings, CiaD was required to induce maximal IL 8 secretion, We also found that the ciaC mutant induced levels of IL 8 secretion indistin guishable from the C. jejuni wild type strain, This finding AG-1478 153436-53-4 suggested that invasion and IL 8 secretion are not directly linked. To address the role of MAP kinase signaling in C. jejuni induction of IL 8 secretion and host cell invasion, assays were performed in the presence of cellular inhibitors to Erk and p38, Inhibition of Erk and p38 resulted in a significant reduction in the number of C.

jejuni internalized and the amount of secreted IL 8, Consistent with these findings, we found that the amount of IL 8 secreted by the host cells inoculated with the CiaD mutant was reduced significantly when the activation of Erk and p38 were inhibited, Specifically, inhibition of Erk results in a 70% reduction in the amount of IL 8 secreted from host cells infected with a C. jejuni wild type strain, similarly inhibition of Erk resulted also in a reduc tion in IL 8 secreted from host cells that were infected with the C. jejuni ciaD mutant. These results are con sistent with the fact that the C. jejuni ciaD mutant ac tivates Erk to a level that is slightly above that of cells only. Moreover, the addition of exogenous IL 8 to Caco 2 cells, an intestinal cell line that is responsive to IL 8 because of the presence of the CXCR1 and CXCR2 receptors, did not restore the invasiveness of the C. jejuni ciaD mutant to that of a C.