Role of Meprins to Protect Ileal Mucosa of Crohn's Disease Patients from Colonization by Adherent-Invasive E. coli

Vazeille, Emilie; Bringer, Marie-Agnès; Gardarin, Aurélie; Chambon, Christophe; Becker‐Pauly, Christoph; Pender, Sylvia L.F.; Jakob, Christine; Müller, Stefan; Lottaz, Daniel; Darfeuille‐Michaud, Arlette

doi:10.1371/journal.pone.0021199

Cited by 41 publications

(35 citation statements)

References 42 publications

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“…AIEC strains LF9. LF15, LF31, and LF82 entered within fully differentiated T84 cells at a level 2.5-fold lower than S. Typhimurium (454). When examining mucosa-associated FimH-positive E. coli strains isolated from IBD and non-IBD pediatric patients for their ability to bind onto fully differentiated Caco-2 cells, the results showed a higher site substitution rate in the fimH gene, which, together with a higher number of mutations, influences the adhesiveness of the strains (457).…”

Section: Cell Interaction Cell Entry and Intracellular Lifestylementioning

confidence: 87%

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Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Moal

Servin

2013

Microbiol Mol Biol Rev

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SUMMARY Hosts are protected from attack by potentially harmful enteric microorganisms, viruses, and parasites by the polarized fully differentiated epithelial cells that make up the epithelium, providing a physical and functional barrier. Enterovirulent bacteria interact with the epithelial polarized cells lining the intestinal barrier, and some invade the cells. A better understanding of the cross talk between enterovirulent bacteria and the polarized intestinal cells has resulted in the identification of essential enterovirulent bacterial structures and virulence gene products playing pivotal roles in pathogenesis. Cultured animal cell lines and cultured human nonintestinal, undifferentiated epithelial cells have been extensively used for understanding the mechanisms by which some human enterovirulent bacteria induce intestinal disorders. Human colon carcinoma cell lines which are able to express in culture the functional and structural characteristics of mature enterocytes and goblet cells have been established, mimicking structurally and functionally an intestinal epithelial barrier. Moreover, Caco-2-derived M-like cells have been established, mimicking the bacterial capture property of M cells of Peyer's patches. This review intends to analyze the cellular and molecular mechanisms of pathogenesis of human enterovirulent bacteria observed in infected cultured human colon carcinoma enterocyte-like HT-29 subpopulations, enterocyte-like Caco-2 and clone cells, the colonic T84 cell line, HT-29 mucus-secreting cell subpopulations, and Caco-2-derived M-like cells, including cell association, cell entry, intracellular lifestyle, structural lesions at the brush border, functional lesions in enterocytes and goblet cells, functional and structural lesions at the junctional domain, and host cellular defense responses.

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Section: Cell Interaction Cell Entry and Intracellular Lifestylementioning

confidence: 87%

“…(ii) AIEC. AIEC strains induce a fimA-dependent basolateral IL-8 secretion in fully differentiated T84 cells (454). A flagellumdependent AIEC O83:H1-induced basolateral secretion of IL-8 and CCL20 has been observed in fully differentiated Caco-2BBe clone cells and T84 cells (449).…”

Section: Host Cellular Defense Responsesmentioning

confidence: 96%

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Moal

Servin

2013

Microbiol Mol Biol Rev

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“…Notably, this specificity for negatively charged amino acid residues in the P1′ site is also characteristic of two other members of the astacin family, meprin α and meprin β (13). Meprin proteases are expressed in a range of tissues, where they activate or release growth factors and other biologically active peptides, and are involved in immunological and neuropathological processes, angiogenesis, and matrix remodeling (14)(15)(16)(17)(18)(19)(20).…”

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confidence: 92%

Metalloproteases meprin α and meprin β are C- and N-procollagen proteinases important for collagen assembly and tensile strength

Broder¹,

Arnold

Goff

et al. 2013

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

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123

102

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Type I fibrillar collagen is the most abundant protein in the human body, crucial for the formation and strength of bones, skin, and tendon. Proteolytic enzymes are essential for initiation of the assembly of collagen fibrils by cleaving off the propeptides. We report that Mep1a −/− and Mep1b −/− mice revealed lower amounts of mature collagen I compared with WT mice and exhibited significantly reduced collagen deposition in skin, along with markedly decreased tissue tensile strength. While exploring the mechanism of this phenotype, we found that cleavage of full-length human procollagen I heterotrimers by either meprin α or meprin β led to the generation of mature collagen molecules that spontaneously assembled into collagen fibrils. Thus, meprin α and meprin β are unique in their ability to process and release both C-and N-propeptides from type I procollagen in vitro and in vivo and contribute to the integrity of connective tissue in skin, with consequent implications for inherited connective tissue disorders.proteolysis | Ehlers-Danlos syndrome | proteomics | fibrosis | connective tissue

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“…In this context, a variety of meprin substrates have been reported in vitro, including biologically active peptides such as gastrin and cholecystokinin, substance P, cytokines, and chemokines (reviewed by Sterchi et al , 2008 ). Of special interest is the fact that meprins cleave components of the extracellular matrix, in particular the basal lamina but also adhesion proteins at the cell-cell interface (Sterchi et al , 2008 ;Ambort et al , 2010 ;Vazeille et al , 2011 ). Recent proteomics approaches have identifi ed previously known and new physiologically relevant in vivo substrates such as vascular endothelial growth factor (Sch ü tte et al, 2010 ), amyloid precursor protein (Jefferson et al , 2011 ), procollagens I and III (Kronenberg et al , 2010 ), interleukin-1 β (Herzog et al , 2005 ), interleukin 18 (Banerjee and Bond , 2008 ), prokallikrein 7 (Ohler et al , 2010 ), and fi broblast growth factor 19 (Becker -Pauly et al, 2011 ).…”

Section: Introduction: a Short Historical Backgroundmentioning

confidence: 99%

Functional and structural insights into astacin metallopeptidases

Gomis‐Rüth

Trillo-Muyo

Stöcker

2012

Biological Chemistry

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The astacins are a family of multi-domain metallopeptidases with manifold functions in metabolism. They are either secreted or membrane-anchored and are regulated by being synthesized as inactive zymogens and also by colocalizing protein inhibitors. The distinct family members consist of N-terminal signal peptides and pro-segments, zincdependent catalytic domains, further downstream extracellular domains, transmembrane anchors, and cytosolic domains. The catalytic domains of four astacins and the zymogen of one of these have been structurally characterized and shown to comprise compact ∼ 200-residue zinc-dependent moieties divided into an N-terminal and a C-terminal sub-domain by an active-site cleft. Astacins include an extended zinc-binding motif (HEXXHXXGXXH) which includes three metal ligands and groups them into the metzincin clan of metallopeptidases. In mature, unbound astacins, a conserved tyrosine acts as an additional zinc ligand, which is swung out upon substrate or inhibitor binding in a ' tyrosine switch ' motion. Other characteristic structural elements of astacin catalytic domains are three large α -helices and a fi ve-stranded β -sheet, as well as two or three disulfi de bonds. The N-terminal pro-segments are variable in length and rather unstructured. They inhibit the catalytic zinc following an ' aspartate-switch ' mechanism mediated by an aspartate embedded in a conserved motif (FXGD). Removal of the pro-segment uncovers a deep and extended active-site cleft, which in general shows preference for aspartate residues in the specifi city pocket (S 1 ′ ). Furthermore, astacins undergo major rearrangement upon activation within an ' activation domain, ' and show a slight hinge movement when binding substrates or inhibitors. In this review, we discuss the overall architecture of astacin catalytic domains and their involvement in function and zymogenic activation.

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Role of Meprins to Protect Ileal Mucosa of Crohn's Disease Patients from Colonization by Adherent-Invasive E. coli

Cited by 41 publications

References 42 publications

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Metalloproteases meprin α and meprin β are C- and N-procollagen proteinases important for collagen assembly and tensile strength

Functional and structural insights into astacin metallopeptidases

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