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Abstract
Intestinal barrier is the first line of defense inside the body and comprises intercellular tight junction (TJ) proteins that regulate paracellular permeability. Deoxynivalenol (DON), a fungal metabolite often found in the contaminated food of domestic animals, is known to impair intestinal barrier function and may be involved in intestinal inflammation. Unlike in humans and mice, the importance of Toll-like receptor (TLR) 2 expressed in porcine intestinal epithelial cells is largely unclear. Therefore, the aim of the present study was to investigate whether TLR2 stimulation enhances intestinal barrier function and protects against DON exposure. We found that the cells treated with TLR2 ligands decreased the epithelial barrier permeability and enhanced TJ protein expression in intestinal porcine epithelial cells (IPEC-J2). In addition, pretreatment with TLR2 ligand, including Pam3CSK4 (PCSK) and lipoteichoic acid from Bacillus subtilis, prevented DON-induced barrier dysfunction by increasing the expression of TJ proteins via the PI3K-Akt-dependent pathway. It is likely that the DON-disrupted intestinal barrier caused biological changes of immune cells in the lamina propria. Thus, we conducted co-culture of differentiated IPEC-J2 cells in the upper well together with peripheral blood mononuclear cells in the bottom well and found that apical TLR2 stimulation of IPEC-J2 cells could alleviate the reduction in cell survival and proliferation of immune cells. Conclusively, TLR2 signaling on intestinal epithelial cells may enhance intestinal barrier function and prevent DON-induced barrier dysfunction of epithelial cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-016-0309-1) contains supplementary material, which is available to authorized users.
Highlights
The gastrointestinal tract is chronically exposed to a huge burden of foreign antigens including microorganisms and toxic molecules
To investigate the effect of DON on epithelial cells, we examined changes in the expression of tight junction (TJ) proteins in IPEC-J2 cells treated with DON
The results showed that TLR2 ligand-mediated expression of claudin-3 and zonula occludens (ZO)-1 was resistant to DON exposure, which was significantly suppressed by PI3K inhibition (Figures 4B and C)
Summary
The gastrointestinal tract is chronically exposed to a huge burden of foreign antigens including microorganisms and toxic molecules. Intestinal epithelial cells (IECs) provide the initial line of mucosal host defense in the intestine. Their ability to act as a physical barrier against antigens, to allow selective absorption of nutrients, and to defend against harmful molecules is crucial for maintaining gut immune homeostasis [1]. Paracellular and intercellular transit of molecules in the intestine is modulated by a complex network of tight junction (TJ) and gap junction linking IECs [2]. TLR2 is known to enhance transepithelial resistance of the IEC barrier through apical redistribution of ZO-1 via protein kinase Cα/δ [3]. Its stimulation efficiently preserves ZO-1-associated barrier integrity of IECs against stressinduced damage, which is critically controlled by the PI3K/Akt-pathway via MyD88 [4]. The precise role of TLR2 in intestinal barrier function in pig remains unclear
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