Expression of IL-23, VEGF and TLR2/TLR4 on Mononuclear Cells after Exposure to <i>Pseudomonas Aeruginosa</i>

Paolillo, Rossella; Carratelli, Caterina Romano; Sorrentino, Sabato; Mazzola, Nello; Mita, Luigi; Rizzo, Antonietta

doi:10.1177/039463201102400414

Cited by 6 publications

(7 citation statements)

References 30 publications

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“…Furthermore, Tang et al noted that activation of Toll‐like receptor‐4 (TLR4) signalling by blood‐borne gram‐negative bacteria led to greater CCM lesion burden in a mouse model of CCM . In addition to activation of TLR4, infection with gram‐negative bacteria can be associated with increased expression of VEGF . Our data are consistent with these observations.…”

Section: Discussionsupporting

confidence: 90%

VEGF signalling enhances lesion burden in KRIT1 deficient mice

DiStefano

Glading

2019

J Cellular Molecular Medi

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The exact molecular mechanisms underlying CCM pathogenesis remain a complicated and controversial topic. Our previous work illustrated an important VEGF signalling loop in KRIT1 depleted endothelial cells. As VEGF is a major mediator of many vascular pathologies, we asked whether the increased VEGF signalling downstream of KRIT1 depletion was involved in CCM formation. Using an inducible KRIT1 endothelial‐specific knockout mouse that models CCM, we show that VEGFR2 activation plays a role in CCM pathogenesis in mice. Inhibition of VEGFR2 using a specific inhibitor, SU5416, significantly decreased the number of lesions formed and slightly lowered the average lesion size. Notably, VEGFR2 inhibition also decreased the appearance of lesion haemorrhage as denoted by the presence of free iron in adjacent tissues. The presence of free iron correlated with increased microvessel permeability in both skeletal muscle and brain, which was completely reversed by SU5416 treatment. Finally, we show that VEGFR2 activation is a common downstream consequence of KRIT1, CCM2 and CCM3 loss of function, though the mechanism by which VEGFR2 activation occurs likely varies. Thus, our study clearly shows that VEGFR2 activation downstream of KRIT1 depletion enhances the severity of CCM formation in mice, and suggests that targeting VEGF signalling may be a potential future therapy for CCM.

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Section: Discussionsupporting

confidence: 90%

VEGF signalling enhances lesion burden in KRIT1 deficient mice

DiStefano

Glading

2019

J Cellular Molecular Medi

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“…In addition, it has been reported that P. aeruginosa infection is associated to stimulation of TLR4 receptors, leading to an activation of the NF-κB pathway [49]. To assess the impact of inulin and FOS on the inflammatory response, the role of the NF-κB and MAPK signalling pathways in the FOS-mediated modulation of macrophages was assessed.…”

Section: Resultsmentioning

confidence: 99%

Fructooligosacharides Reduce Pseudomonas aeruginosa PAO1 Pathogenicity through Distinct Mechanisms

et al. 2014

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Pseudomonas aeruginosa is ubiquitously present in the environment and acts as an opportunistic pathogen on humans, animals and plants. We report here the effects of the prebiotic polysaccharide inulin and its hydrolysed form FOS on this bacterium. FOS was found to inhibit bacterial growth of strain PAO1, while inulin did not affect growth rate or yield in a significant manner. Inulin stimulated biofilm formation, whereas a dramatic reduction of the biofilm formation was observed in the presence of FOS. Similar opposing effects were observed for bacterial motility, where FOS inhibited the swarming and twitching behaviour whereas inulin caused its stimulation. In co-cultures with eukaryotic cells (macrophages) FOS and, to a lesser extent, inulin reduced the secretion of the inflammatory cytokines IL-6, IL-10 and TNF-α. Western blot experiments indicated that the effects mediated by FOS in macrophages are associated with a decreased activation of the NF-κB pathway. Since FOS and inulin stimulate pathway activation in the absence of bacteria, the FOS mediated effect is likely to be of indirect nature, such as via a reduction of bacterial virulence. Further, this modulatory effect is observed also with the highly virulent ptxS mutated strain. Co-culture experiments of P. aeruginosa with IEC18 eukaryotic cells showed that FOS reduces the concentration of the major virulence factor, exotoxin A, suggesting that this is a possible mechanism for the reduction of pathogenicity. The potential of these compounds as components of antibacterial and anti-inflammatory cocktails is discussed.

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“…21 After BS-14 stimulation, TLR2 was mainly expressed on precursor B cells at 72 h. Some of the bacteria contained in BS-14 can induce TLR2, such as Klebsiella pneumonia and Pseudomonas sp. 16,[22][23][24] Remarkably, it has been reported that some TLR2 ligands induce IL-10, thereby leading to activation of regulatory B cells and the attenuation of T effector functions, which contribute to immune regulation. 25 It is possible that BS-14 stimulation functionally expands a subgroup of Bregs characterized by TLR2 expression and IL-10 production.…”

Section: Discussionmentioning

confidence: 99%

Activation of IL-10+ B cells: A novel immunomodulatory mechanism for therapeutic bacterial suspensions

et al. 2020

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Objectives: Bacterial components are used to improve immune responses in patients with respiratory infections. Pharmacological formulations of bacterial components include a mixture of bacterial antigens, some of which are complete inactivated bacteria, that is, named bacterial suspensions; while others are fragments of bacteria, which are presented as bacterial lysates. Although bacterial lysates have been broadly used as immune-stimulators, the biological support for the therapeutic effectiveness of bacterial suspension has not yet been studied. Thus, the aim of our study was to investigate the immunological activity induced by bacterial suspension. Methods: This work was an exploratory translational study. Peripheral blood mononuclear cells were obtained from healthy donors and cultured in time–dose dependent assays with a commercial bacterial suspension. Flow cytometry was used for phenotypic analysis and for determining soluble cytokines in culture supernatants. Results: We observed that bacterial suspension activates B cells in a dose-dependent manner. Peripheral blood mononuclear cells were able to secrete IL-6 and IL-10 after 24 h of bacterial suspension stimulation. TLR2 expression was observed mainly on CD19+ CD38Lo B cells after 72 h of culture; remarkably, most of the TLR2+ CD19+ cells were also IL-10+. Conclusion: Our findings suggest that bacterial suspension induces the activation of B cell subsets as well as the secretion of IL-6 and IL-10. Expression of TLR2 on CD19+ cells could act as an activation loop of IL-10+ B regulatory cells. The clinical implications of these findings are discussed at the end of this article.

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Expression of IL-23, VEGF and TLR2/TLR4 on Mononuclear Cells after Exposure to Pseudomonas Aeruginosa

Cited by 6 publications

References 30 publications

VEGF signalling enhances lesion burden in KRIT1 deficient mice

VEGF signalling enhances lesion burden in KRIT1 deficient mice

Fructooligosacharides Reduce Pseudomonas aeruginosa PAO1 Pathogenicity through Distinct Mechanisms

Activation of IL-10+ B cells: A novel immunomodulatory mechanism for therapeutic bacterial suspensions

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