Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism

Yan, Fang; Cao, Hanwei; Cover, Timothy L.; Washington, Mary Kay; Shi, Yan; Liu, LinShu; Chaturvedi, Rupesh; Peek, Richard M.; Wilson, Keith T.; Polk, D. Brent

doi:10.1172/jci44031

Cited by 305 publications

(304 citation statements)

References 56 publications

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“…Administration of p40-containing beads to mice specifically delivered p40 to the colon site, which activated epidermal growth factor receptor (EGFR) in colon epithelial cells, reduced intestinal epithelial apoptosis and disruption of barrier function in the colon epithelium, and prevented dextran sulfate sodium-induced intestinal injury and acute colitis, as well as oxazolone-induced Th2 cytokine-derived chronic colitis in C57BL/6 mice (Figure 5a-c). These results provide evidence that the administration of pectin/Ca ++ /zein containing p40 has beneficial effect on the prevention and treatment of intestinal inflammatory disorders [37]. Figure 4.…”

Section: Pectin and Pectin/zeinmentioning

confidence: 73%

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Hydrogels from Biopolymer Hybrid for Biomedical, Food, and Functional Food Applications

et al. 2012

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Hybrid hydrogels from biopolymers have been applied for various indications across a wide range of biomedical, pharmaceutical, and functional food industries. In particular, hybrid hydrogels synthesized from two biopolymers have attracted increasing attention. The inclusion of a second biopolymer strengthens the stability of resultant hydrogels and enriches its functionalities by bringing in new functional groups or optimizing the micro-environmental conditions for certain biological and biochemical processes. This article presents approaches that have been used by our groups to synthesize biopolymer hybrid hydrogels for effective uses for immunotherapy, tissue regeneration, food and functional food applications. The research has achieved some challenging results, such as stabilizing physical structure, increasing mucoadhesiveness, and the creation of an artificial extracellular matrix to aid in guiding tissue differentiation.

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Section: Pectin and Pectin/zeinmentioning

confidence: 73%

“…The white arrow in (B) indicates EGFR-Tyr1068 phosphorylation in cells staining positively for E-cadherin. Colon epithelial cells were isolated for Western blot analysis to detect EGFR and Akt activation [37].…”

Section: Pectin and Pectin/zeinmentioning

confidence: 99%

Hydrogels from Biopolymer Hybrid for Biomedical, Food, and Functional Food Applications

et al. 2012

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“…Transfer of WT macrophages into Akt1 −/− mice reduced the severity of the disease whereas transfer of Akt1 −/− macrophages into WT mice did not worsen it, suggesting that additional cell types deficient in Akt1 may contribute to the increased susceptibility of Akt1 −/− mice to the disease (Fig. 4 E-H), such as intestinal epithelial cells in which Akt protects from cytokine-induced apoptosis (19). The expression of Arg1 and the M2 polarization of macrophages are regulated primarily by C/EBPβ and STAT6 (3,4).…”

Section: Resultsmentioning

confidence: 99%

Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization

Arranz

Doxaki²,

Vergadi³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

484

449

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Activated macrophages are described as classically activated or M1 type and alternatively activated or M2 type, depending on their response to proinflammatory stimuli and the expression of genetic markers including iNOS, arginase1, Ym1, and Fizz1. Here we report that Akt kinases differentially contribute to macrophage polarization, with Akt1 ablation giving rise to an M1 and Akt2 ablation resulting in an M2 phenotype. Accordingly, Akt2 −/− mice were more resistant to LPS-induced endotoxin shock and to dextran sulfate sodium (DSS)-induced colitis than wild-type mice, whereas Akt1 −/− mice were more sensitive. Cell depletion and reconstitution experiments in a DSS-induced colitis model confirmed that the effect was macrophage-dependent. Gene-silencing studies showed that the M2 phenotype of Akt2 −/− macrophages was cell autonomous. The microRNA miR-155, whose expression was repressed in naive and in LPS-stimulated Akt2 −/− macrophages, and its target C/EBPβ appear to play a key role in this process. C/EBPβ, a hallmark of M2 macrophages that regulates Arg1, was up-regulated upon Akt2 ablation or silencing. Overexpression or silencing of miR-155 confirmed its central role in Akt isoform-dependent M1/M2 polarization of macrophages.inflammation | peritonitis | sepsis | inflammatory bowel disease A ctivated macrophages express proinflammatory factors and are known as classically activated or M1-type macrophages. Toll-like receptor (TLR) stimulation may induce the M1 phenotype through the activation of several signaling cascades, which regulate the induction of proinflammatory mediators such as TNF-α, IL-6, and iNOS. However, macrophages can also undergo alternative activation to become alternatively activated or M2-type macrophages. M2 macrophages are characterized by reduced responsiveness to TLR ligands, which results in the induction of low levels of proinflammatory cytokines and in the upregulation of arginase 1 (Arg1), IL-10, found in inflammatory zone 1 (Fizz1), and chitinase 3-like-3 (YM1/CHI3l3) (1). Although the molecular mechanisms that regulate M2 macrophage polarization are not well understood, it appears that STAT6 activation and the induction of C/EBPβ play a central role in this process (2-4). C/EBPβ regulates the expression of Arg1 (3), the gene that encodes the inducible arginase, and selective inhibition of C/EBPβ in macrophages blocks M2 polarization (4).Akt (also known as PKB) is a family of three serine/threonine protein kinases (Akt1, Akt2, and Akt3) that regulate a host of cellular functions, including cell survival, proliferation, differentiation, and intermediary metabolism (5-7). Even though the majority of the literature does not make a distinction between different Akt isoforms, there is a growing list of differences between them. Akt1 appears not to be dispensable for eNOS induction and endothelial cell function (8, 9), whereas Akt2 is not dispensable for insulin signaling (10). Deletion of Akt1 resulted in enhanced atherosclerosis in the APOE −/− mouse model (5), and Akt1 −/− mice do not d...

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“…Some specific probiotic strains altered the expression of tight junction proteins including occludin, cingulin, claudin-2 and ZO-2. 8,9 Evidence also suggests that commensal and probiotic organisms bolstered additional aspects that contribute to intestinal barrier function 6,8,10 including increased IgA production, mucin expression, prevention of intestinal epithelial cell apoptosis, 11 inhibition of colonization by enteric pathogens and the immune response. Specific Lactobacillus strains upregulated the expression of key intestinal epithelial transporters such as the apical anion exchanger SLC26A3 (DRA) responsible for the bulk of Cl -absorption by the gut 12,13 ( Fig.…”

Section: Introductionmentioning

confidence: 99%

The intestinal microbiome, probiotics and prebiotics in neurogastroenterology

Saulnier¹,

et al. 2013

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The brain-gut axis allows bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent experimental work suggests that the gut microbiota have an impact on the brain-gut axis. A group of experts convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) discussed the role of gut bacteria on brain functions and the implications for probiotic and prebiotic science. The experts reviewed and discussed current available data on the role of gut microbiota on epithelial cell function, gastrointestinal motility, visceral sensitivity, perception and behavior. Data, mostly gathered from animal studies, suggest interactions of gut microbiota not only with the enteric nervous system but also with the central nervous system via neural, neuroendocrine, neuroimmune and humoral links. Microbial colonization impacts mammalian brain development in early life and subsequent adult behavior. These findings provide novel insights for improved understanding of the potential role of gut microbial communities on psychological disorders, most particularly in the field of psychological comorbidities associated with functional bowel disorders like irritable bowel syndrome (IBS) and should present new opportunity for interventions with pro-and prebiotics.

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Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism

Cited by 305 publications

References 56 publications

Hydrogels from Biopolymer Hybrid for Biomedical, Food, and Functional Food Applications

Hydrogels from Biopolymer Hybrid for Biomedical, Food, and Functional Food Applications

Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization

The intestinal microbiome, probiotics and prebiotics in neurogastroenterology

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