Clostridium difficile -derived membrane vesicles induce the expression of pro-inflammatory cytokine genes and cytotoxicity in colonic epithelial cells in vitro

Nicholas, Asiimwe; Jeon, Hyejin; Selasi, Gati Noble; Na, Seok Hyeon; Kwon, Hyo Il; Kim, Yoo Jeong; Choi, Chi Won; Kim, Kyung Sik; Lee, Je Chul

doi:10.1016/j.micpath.2017.03.006

Cited by 21 publications

(28 citation statements)

References 39 publications

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“…Pro-inflammatory cytokines are secreted from the endothelium and immunocytes in response to various stimuli ( 31 , 32 ). The total number of leukocytes, neutrophils, macrophages and lymphocytes in BALF was assessed.…”

Section: Resultsmentioning

confidence: 99%

Recombinant club cell protein 16 (CC16) ameliorates cigarette smoke‑induced lung inflammation in a murine disease model of COPD

Pang

Liu

et al. 2018

Mol Med Report

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Club cell protein (CC16) is expressed primarily by club cells possesses anti-inflammatory properties and is located in the bronchiolar epithelium. Previous studies have demonstrated that CC16 deficiency is associated with the progression of chronic obstructive pulmonary disease (COPD). In the present study, the therapeutic effects of recombinant rat CC16 protein in mice with COPD were examined and the underlying mechanisms investigated. A total of 30 adult male C57/BL6 mice were randomly divided into three groups (10 mice/group). A mouse COPD model was generated by exposing 20 mice to cigarette smoke (CS) for 24 weeks. A total of 10 mice were treated intranasally with rCC16 (2.5 µg/g body weight) and control mice were exposed to normal room air. Results indicated that rCC16 treatment ameliorated pathological damage in the lungs and reduced the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8, which were induced by CS exposure. After rCC16 administration, endogenous CC16 was upregulated and the body weight of COPD mice was increased, whereas the opposite was observed in CS-exposed mice. Additionally, rCC16 treatment inhibited the DNA binding of NF-κB/p65 in lung tissues and reduced nuclear translocation of NF-κB/p65 in BALF and epithelial cells. Moreover, rCC16 treatment lead to a decrease in the total number of BALF cells, including macrophages, which was elevated in COPD mice. In conclusion, the present results demonstrate that rCC16 has therapeutic effects on COPD by downregulating pro-inflammatory factors via the NF-κB pathway.

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Section: Resultsmentioning

confidence: 99%

Recombinant club cell protein 16 (CC16) ameliorates cigarette smoke‑induced lung inflammation in a murine disease model of COPD

Pang

Liu

et al. 2018

Mol Med Report

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“…Interestingly, in Clostridium difficile infection, phage transfer during fecal transplantation is associated with treatment outcome, even though there is no evidence that phages specific for that pathogen are being transferred [ 27 , 28 ]. It is known that C. difficile causes colitis by inducing the expression of proinflammatory cytokines and cytotoxicity in colonic IEC in vitro and in vivo [ 29 , 30 ]. Thus, the beneficial role of phages in this clinical setting may be associated primarily with their anti-inflammatory action at the level of IEC.…”

Section: Bacteriophages As Potential Immunomodulators Of Iec-dependenmentioning

confidence: 99%

Bacteriophages targeting intestinal epithelial cells: a potential novel form of immunotherapy

Górski

Jończyk‐Matysiak

Łusiak-Szelachowska

et al. 2017

Cell. Mol. Life Sci.

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In addition to their established role as a physical barrier to invading pathogens and other harmful agents, intestinal epithelial cells (IEC) are actively involved in local immune reactions. In the past years, evidence has accumulated suggesting the role of IEC in the immunopathology of intestinal inflammatory disorders (IBD). Recent advances in research on bacteriophages strongly suggest that—in addition to their established antibacterial activity—they have immunomodulating properties that are potentially useful in the clinic. We suggest that these immunomodulating phage activities targeting IEC may open novel treatment perspectives in disorders of the alimentary tract, particularly IBD.

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“…OMVs enhance bacterial pathogenesis by delivery of virulence factors to host cells, biofilm formation, increased antimicrobial resistance, and modulation of innate immune responses (Kuehn and Kesty, 2005; Kulp and Kuehn, 2010). Membrane vesicles (MVs) derived from gram-positive bacteria have been discovered in Staphylococcus aureus, Bacillus spp., Clostridium spp., and Listeria monocytogenes (Lee et al, 2009, 2013; Rivera et al, 2010; Gurung et al, 2011; Nicholas et al, 2017). MVs derived from gram-positive pathogens are potent facilitators of host-pathogen interactions via transport of virulence factors and modulation of immune response, similar to OMVs from gram-negative pathogens (Rivera et al, 2010; Gurung et al, 2011; Thay et al, 2013; Nicholas et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Membrane vesicles (MVs) derived from gram-positive bacteria have been discovered in Staphylococcus aureus, Bacillus spp., Clostridium spp., and Listeria monocytogenes (Lee et al, 2009, 2013; Rivera et al, 2010; Gurung et al, 2011; Nicholas et al, 2017). MVs derived from gram-positive pathogens are potent facilitators of host-pathogen interactions via transport of virulence factors and modulation of immune response, similar to OMVs from gram-negative pathogens (Rivera et al, 2010; Gurung et al, 2011; Thay et al, 2013; Nicholas et al, 2017). The biogenesis of bacterial extracellular vesicles is still poorly understood, but stressful environments such as growth temperature, envelope stress, or oxidizing agents have been shown to increase their production (Mug-Opstelten and Witholt, 1978; Katsui et al, 1982; Thompson et al, 1985; McBroom and Kuehn, 2007).…”

Section: Introductionmentioning

confidence: 99%

Production of Membrane Vesicles by Enterococcus faecium Cultured With or Without Subinhibitory Concentrations of Antibiotics and Their Pathological Effects on Epithelial Cells

Kim

Son

et al. 2019

Front. Cell. Infect. Microbiol.

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Enterococcus faecium is a clinically important pathogen associated with opportunistic infection and multi-drug resistance. E. faecium has been shown to produce membrane vesicles (MVs), but MV production by E. faecium under antibiotic stress conditions and the pathogenic traits thereof have yet to be determined. This study investigated the production of MVs in E. faecium ATCC 700221 cultured with sub-minimum inhibitory concentrations (MICs) of vancomycin or linezolid and determined their pathologic effects on colon epithelial Caco-2 cells. E. faecium ATCC 700221 cultured with 1/2 MIC of vancomycin or linezolid produced 3.0 and 1.5 times more MV proteins than bacteria cultured without antibiotics, respectively. Totals of 438, 461, and 513 proteins were identified in MVs from E. faecium cultured in brain heart infusion broth (MVs/BHI), BHI broth with 1/2 MIC of vancomycin (MVs/VAN), or BHI broth with 1/2 MIC of linezolid (MVs/LIN), respectively. Intact MVs/BHI induced cytotoxicity and the expression of pro-inflammatory cytokine and chemokine genes in Caco-2 cells in a dose-dependent manner, but proteinase K-treated MVs significantly suppressed these pro-inflammatory responses. MVs/LIN were more cytotoxic toward Caco-2 cells than MVs/BHI and MVs/VAN, whereas MVs/VAN stimulated more pro-inflammatory cytokine gene expression in Caco-2 cells than MVs/BHI and MVs/LIN. Overall results indicated that antibiotics modulate the biogenesis and proteomes of MVs in E. faecium at subinhibitory concentrations. MVs produced by E. faecium cultured under antibiotic stress conditions induce strong host cell responses that may contribute to the pathogenesis E. faecium .

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Clostridium difficile -derived membrane vesicles induce the expression of pro-inflammatory cytokine genes and cytotoxicity in colonic epithelial cells in vitro

Cited by 21 publications

References 39 publications

Recombinant club cell protein 16 (CC16) ameliorates cigarette smoke‑induced lung inflammation in a murine disease model of COPD

Recombinant club cell protein 16 (CC16) ameliorates cigarette smoke‑induced lung inflammation in a murine disease model of COPD

Bacteriophages targeting intestinal epithelial cells: a potential novel form of immunotherapy

Production of Membrane Vesicles by Enterococcus faecium Cultured With or Without Subinhibitory Concentrations of Antibiotics and Their Pathological Effects on Epithelial Cells

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