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Bifidobacteria are extensively exploited for the formulation of probiotic food supplements due to their claimed ability to exert health-beneficial effects upon their host. However, most commercialized probiotics are tested and selected for their safety features rather than for their effective abilities to interact with the host and/or other intestinal microbial players. In this study, we applied an ecological and phylogenomic-driven selection to identify novel B. longum subsp. longum strains with a presumed high fitness in the human gut. Such analyses allowed the identification of a prototype microorganism to investigate the genetic traits encompassed by the autochthonous bifidobacterial human gut communities. B. longum subsp. longum PRL2022 was selected due to its close genomic relationship with the calculated model representative of the adult human-gut associated B. longum subsp. longum taxon. The interactomic features of PRL2022 with the human host as well as with key representative intestinal microbial members were assayed using in vitro models, revealing how this bifidobacterial gut strain is able to establish extensive cross-talk with both the host and other microbial residents of the human intestine. [ABSTRACT FROM AUTHOR]

Amorphous silica nanoparticles (ASNP) are present in a variety of products and their biological effects are actively investigated. Although several studies have documented pro-inflammatory effects of ASNP, the possibility that they also modify the response of innate immunity cells to natural activators has not been thoroughly investigated. Here, we study the effects of pyrogenic ASNP on the LPS-dependent activation of human macrophages differentiated from peripheral blood monocytes. In macrophages, 24 h of pre-exposure to non-cytotoxic doses of ASNP markedly inhibited the LPS-dependent induction of pro-inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10). The inhibitory effect was associated with the suppression of NFκB activation and the increased intracellular sequestration of the TLR4 receptor. The late induction of glutamine synthetase (GS) by LPS was also prevented by pre-exposure to ASNP, while GS silencing did not interfere with cytokine secretion. It is concluded that (i) macrophages exposed to ASNP are less sensitive to LPS-dependent activation and (ii) GS induction by LPS is likely secondary to the stimulation of cytokine secretion. The observed interference with LPS effects may point to a dampening of the acute inflammatory response after exposure to ASNP in humans. [ABSTRACT FROM AUTHOR]

Previous work has demonstrated that precipitated (NM-200) and pyrogenic (NM-203) Amorphous Silica Nanoparticles (ASNPs) elicit the inflammatory activation of murine macrophages, with more pronounced effects observed with NM-203. Here, we compare the effects of low doses of NM-200 and NM-203 on human macrophage-like THP-1 cells, assessing how the pre-exposure to these nanomaterials affects the cell response to lipopolysaccharide (LPS). Cell viability was affected by NM-203, but not by NM-200, and only in the presence of LPS. While NM-203 stimulated mTORC1, neither ASNPs activated NFκB or the transcription of its target genes PTGS2 and IL1B. NM-200 and NM-203 caused a block of the autophagic flux and inhibited the LPS-dependent increase of Glutamine Synthetase (GS) expression. Both ASNPs suppressed the activation of caspase-1, delaying the LPS-dependent secretion of IL-1β. Thus, ASNPs modulate several important pathways in human macrophages, altering their response to LPS. NM-203 had larger effects on autophagy, mTORC1 activity and GS expression than NM-200, confirming the higher biological activity of pyrogenic ASNPs when compared with precipitated ASNPs. [ABSTRACT FROM AUTHOR]

The possibility of counteracting inflammation-related barrier defects with dietary compounds such as (poly)phenols has raised much interest, but information is still scarce. We have investigated here if (+)-catechin (CAT) and procyanidin B2 (PB2), two main dietary polyphenols, protect the barrier function of intestinal cells undergoing inflammatory stress. The cell model adopted consisted of co-cultured Caco-2 and HT29-MTX cells, while inflammatory conditions were mimicked through the incubation of epithelial cells with the conditioned medium of activated macrophages (MCM). The epithelial barrier function was monitored through trans-epithelial electrical resistance (TEER), and ROS production was assessed with dichlorofluorescein, while the expression of tight-junctional proteins and signal transduction pathways were evaluated with Western blot. The results indicated that MCM produced significant oxidative stress, the activation of NF-κB and MAPK pathways, a decrease in occludin and ZO-1 expression, and an increase in claudin-7 (CL-7) expression, while TEER was markedly lowered. Neither CAT nor PB2 prevented oxidative stress, transduction pathways activation, ZO-1 suppression, or TEER decrease. However, PB2 prevented the decrease in occludin expression and both polyphenols produced a huge increase in CL-7 abundance. It is concluded that, under the conditions adopted, CAT and PB2 do not prevent inflammation-dependent impairment of the epithelial barrier function of intestinal cell monolayers. However, the two compounds modify the expression of tight-junctional proteins and, in particular, markedly increase the expression of CL-7. These insights add to a better understanding of the potential biological activity of these major dietary flavan-3-ols at intestinal level. [ABSTRACT FROM AUTHOR]

Multi-walled carbon nanotubes (MWCNT) have many outstanding physical and chemical properties that make them useful in many applications in nanotechnology. However, these properties are reported to be potentially harmful for the human body. The effects of low and realistic doses of three well-characterized preparations of MWCNT, obtained from the Joint Research Centre (JRC) (NM-400, NM-401, and NM-402), were assessed in two murine macrophage lines, Raw264.7, of peritoneal origin, and MH-S, derived from alveolar macrophages. Macrophage viability, evaluated with two distinct methods, was significantly lowered by NM-401 (needle-like, average length 4 μm, diameter 67 nm) with IC50 values of 10 μg/cm2, whereas NM-400 and NM-402 (tangled, average lengths 846–1372 nm, diameter 11 nm) had much smaller effects. In contrast, at 10 μg/cm2, NM-400 and NM-402 induced the M1 marker Nos2 and, consistently, a sizable accumulation of nitrites in the medium, whereas NM-401 had no significant effect. None of the MWCNT preparations induced the M2 marker Arg1. Phagocytic activity, assessed in Raw264.7 macrophages, was significantly reduced in cells exposed to NM-401, but not to NM-400 or NM-402. When tested on Calu-3 bronchial epithelial cell monolayers, the three MWCNT preparations did not affect cell viability, but decreased the trans-epithelial electrical resistance at the maximal dose tested (80 μg/cm2), with the most evident effect detected for NM-401, even at 10 μg/cm2. In conclusion, among the possible structural determinants of the toxic effects exerted by MWCNT towards macrophages and airway epithelial cells, shape and length appear the most relevant at low, realistic doses. [ABSTRACT FROM AUTHOR]