IECs, in addition to their metabolic functions, play a major role in the generation of innate immunity. To explore this function of IECs, we used a murine epithelial cell line (MODE-K)

derived from the small intestine [24]. We found that the two L. gasseri this website strains differentially influenced MODE-K cells. In particular, OLL2809 was more effective than L13-Ia in stimulating IL-6 secretion without inducing surface expression of MHC class II molecules. However, L13-Ia induced the expression of MHC click here class II, a phenomenon that allows IECs to stimulate CD4+ T cells during inflammation or in response to infection. Moreover, only SupOLL2809 induced IL-6 secretion in MODE-K cells, thus further highlighting the existence of distinctive BAY 11-7082 solubility dmso responses elicited by these strains. The biological significance of the IL-6 increase remains controversial because this cytokine has both pro-and anti-inflammatory activities.

Its receptor, IL-6R, is expressed on the surface of only a few cell types including hepatocytes and some leukocytes. The IL-6/IL-6R complex associates with gp130, which dimerizes and initiates intracellular signaling that triggers anti-inflammatory activities, such as inhibition of apoptosis and a parallel induction of proliferation in IECs [39]. However, IL-6 trans-signaling appears to mediate the pro-inflammatory activity of this cytokine, a process involving the binding of the soluble form of IL-6R to gp130 on cells that do not express IL-6R [39]. Our findings suggest that OLL2809 might contribute to gut immune homeostasis better than L13-Ia. Moreover, our results strengthen the concept that a probiotic activity can be induced not only from whole microorganisms and cell wall components but also from secreted metabolites. Stabilization of the enterocyte cytoskeleton was found to be mediated by a protease-sensitive metabolite secreted by the probiotic mixture VSL#3 [40]. More recently, exposure to probiotic-conditioned media was shown to attenuate the inflammatory responses induced in different enterocyte models [41].

In the intestinal lamina propria, DCs are classically immature DCs that, following antigen encounter, Sclareol migrate into mesenteric lymph nodes where they are primed. The existence of IEC-DC crosstalk has been suggested by observations showing that IECs can drive differentiation of Treg cell-promoting DCs. This differentiation is mediated by IEC-secreted transforming growth factor-β and retinoic acid [42]. In agreement with these findings, we confirmed that medium conditioned by unstimulated MODE-K cells induced a regulatory phenotype in DCs, as shown by the reduced surface expression of co-stimulatory markers and, most importantly, reversal of the IL-12/IL-10 ratio. In the presence of a pro-inflammatory stimulus (i.e., treatment with TNF-α), this regulatory phenotype was abrogated, confirming that IEC-DC crosstalk is highly regulated. We further addressed this issue by evaluating the ability of L.