Several previous studies have demonstrated that some helminth infections can inhibit allergic reactions, but the examination on the effect of live Schistosoma japonicum (SJ) infection on allergic inflammation remains limited. The aim of this study was to examine the effect and mechanism of chronic SJ infection on airway allergic inflammation in a murine model. The data showed that chronic SJ infection suppressed airway eosinophilia, mucus production and antigen-specific IgE responses induced by ovalbumin (OVA) sensitization and challenge. Cytokine production analysis showed that chronic SJ infection reduced allergen-driven interleukin (IL)-4 and IL-5 production, but had no significant effect on IFN-gamma production. More importantly, we found that the adoptive transfer of dendritic cells (DCs) from SJ-infected mice dramatically decreased airway allergic inflammation in the recipients, which was associated with significant decrease of IL-4/IL-5 production and increase of IL-10 production. The results suggest that SJ infection may inhibit the development of allergy and that DCs may be involved in the process of helminth infection-mediated modulation of allergic inflammation.

Bifico is a probiotic mixture containing Bifidobacterium, Lactobacillus acidophilus, and Enterococcus. Studies support that Bifico has a protective effect in experimental colitis (IL-10-deficient and TNBS) models and in patients with inflammatory bowel disease (IBD). However, the mechanism underlying the protective effects of this mixture of probiotic bacteria remains incompletely clear. Here, we investigated the effect of Bifico on intestinal inflammation. In an in vivo experiment, dextran sulfate sodium was used to induce colitis. Bifico treatment significantly attenuated the severity of colitis in this model. Bifico increased the expression of tight junction proteins (TJs). In addition, Bifico increased the number of Tregs, but reduced the number of total CD4+ T cells in the peripheral blood. Furthermore, the expression of colonic CD4 protein was decreased while the level of forkhead box P3 (Foxp3) was upregulated. These results suggested that Bifico exerts beneficial effects on experimental colitis by increasing the expressions of TJs, upregulating the number of Tregs, and reducing the total CD4+ T cell number in both colon and peripheral blood. The intestinal damage in the pretreated + treated-Bifico-colitis group was more severe than that in only the pretreated-Bifico-colitis group. This suggested that Bifico might aggravate intestinal damage when the mucosal barrier is impaired.

Focal adhesions are specialized sites of cell attachment to the extracellular matrix where integrin receptors link extracellular matrix to the actin cytoskeleton, and they are constantly remodeled during cell migration. Focal adhesion kinase (FAK) is an important regulator of focal adhesion remodeling. AGAP2 is an Arf GTPase-activating protein that regulates endosomal trafficking and is overexpressed in different human cancers. Here we examined the regulation of the FAK activity and the focal adhesion remodeling by AGAP2. Our results show that FAK binds the pleckstrin homology domain of AGAP2, and the binding is independent of FAK activation following epidermal growth factor receptor stimulation. Overexpression of AGAP2 augments the activity of FAK, and concordantly, the knockdown of AGAP2 expression with RNA interference attenuates the FAK activity stimulated by epidermal growth factor or plateletderived growth factor receptors. AGAP2 is localized to the focal adhesions, and its overexpression results in dissolution of the focal adhesions, whereas knockdown of its expression stabilizes them. The AGAP2-induced dissolution of the focal adhesions is independent of its GTPase-activating protein activity but may involve its N-terminal G protein-like domain. Our results indicate that AGAP2 regulates the FAK activity and the focal adhesion disassembly during cell migration.Focal adhesions are macromolecular structures that connect actin cytoskeleton to the extracellular matrix and play an important role in cell migration (1). Components of focal adhesions include signaling proteins such as focal adhesion kinase (FAK), 3 c-Src, and paxillin, as well as structural proteins such as talin and vinculin (2, 3). Focal adhesions are constantly formed and disassembled (i.e. remodeled) at the leading edge of migrating cells, and they are disassembled at the trailing edge during the cell migration (4, 5). Available evidence demonstrates that the remodeling of focal adhesions is regulated by FAK (6) and Arf-directed GTPase-activating proteins (Arf GAPs) (7).FAK is a member of the Src family nonreceptor tyrosine kinases whose activities are regulated by intra-molecular phosphorylation (8). Autophosphorylation of FAK on tyrosine residue 397 provides docking sites for Src homology 2 domain-containing proteins, including c-Src. After binding to FAK, c-Src phosphorylates FAK on Tyr-576 and Tyr-577 to activate fully the intrinsic kinase activity of FAK (9). Cellular functions of FAK are many and include cell migration, survival, and proliferation; and activation of FAK occurs upon integrin clustering or stimulation of cell surface receptors such as the epidermal growth factor (EGF) or plateletderived growth factor (PDGF) receptors. FAK activation following integrin clustering results in recruitment of structural and signaling proteins that collectively contribute to the formation of the focal adhesions (10). In FAK null cells, focal adhesions are formed but cannot disassemble (11), suggesting that FAK is required for the focal adhesion...

No abstract