Elevated Expression of Paneth Cell CRS4C in Ileitis-prone SAMP1/YitFc Mice

Shanahan, Michael T.; Vidrich, Alda; Shirafuji, Yoshinori; Dubois, Claire L.; Henschen-Edman, Agnes H.; Hagen, Susan J.; Cohn, Steven M.

doi:10.1074/jbc.m109.083220

Cited by 18 publications

(17 citation statements)

References 69 publications

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“…α-Defensins induce the formation of ion channels in lipid bilayers [74], and peptide-elicited effects are influenced by cell and membrane energetics [30]. Peptide-induced efflux of potassium ions from bacterial cells is a sensitive indicator of membrane disruption and cell death [75–77], and extracellular K + levels increase markedly and almost immediately when bacteria are exposed to varied Paneth cell α-defensins [64, 78]. …”

Section: Mechanisms Of α-Defensin Bactericidal Actionmentioning

confidence: 99%

“…In human, rat, mouse, and monkey small intestine, α-defensin transcripts and peptides occur only in Paneth cells, with peptides localizing to dense core secretory granules [78, 97–99, 101–103]. In contrast to the numerous and diverse α-defensin genes expressed by mouse and macaque Paneth cells, humans make only two Paneth cell α-defensins, HD5 and HD6 (Figure 3) [103–107].…”

Section: α-Defensin Distribution and Gene Expressionmentioning

confidence: 99%

“…In mice, and only in mice, α-defensin-related genes code for two subfamilies of Cysteine-Rich Sequence (CRS) peptides, CRS1C and CRS4C [78, 149–153]. Also expressed specifically by Paneth cells, CRS and Crp mRNA levels in Paneth cells are approximately the same, and the concentrations of both mRNA subfamilies increase coordinately during postnatal crypt ontogeny [154].…”

Section: Mouse α-Defensin Genomicsmentioning

confidence: 99%

“…CRS4C-coding genes exhibit a regional expression pattern, with highest CRS4C mRNA levels in ileum with nearly undetectable levels in proximal small intestine [78]. CRS4C-1 peptides also occur in Paneth cell dense core granules, and thus are secreted to function in the intestinal lumen.…”

Section: Mouse α-Defensin Genomicsmentioning

confidence: 99%

“…CRS4C-1 peptides also occur in Paneth cell dense core granules, and thus are secreted to function in the intestinal lumen. CRS4C bactericidal peptide activity is membrane disruptive in that it permeabilizes E. coli and induces rapid microbial cell K + efflux, but in a manner different from mouse α-defensin cryptdin-4 [78]. In vitro , inactive pro-CRS4C-1 is converted to bactericidal CRS4C-1 peptide by MMP7 proteolysis of the precursor proregion at the same residue positions that MMP7 activates mouse pro-α-defensins.…”

Section: Mouse α-Defensin Genomicsmentioning

confidence: 99%

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Paneth cell α-defensins in enteric innate immunity

Ouellette

2011

Cell. Mol. Life Sci.

135

138

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Paneth cells at the base of small intestinal crypts of Lieberkühn secrete high levels of α-defensins in response to cholinergic and microbial stimuli. Paneth cell α-defensins are broad spectrum microbicides that function in the extracellular environment of the intestinal lumen, and they are responsible for the majority of secreted bactericidal peptide activity. Paneth cell α-defensins confer immunity to oral infection by Salmonella enterica serovar Typhimurium, and they are major determinants of the composition of the small intestinal microbiome. In addition to host defense molecules such as α-defensins, lysozyme, and Pla2g2a, Paneth cells also produce and release proinflammatory mediators as components of secretory granules. Disruption of Paneth cell homeostasis, with subsequent induction of endoplasmic reticulum (ER) stress, autophagy, or apoptosis, contributes to inflammation in diverse genetic and experimental mouse models.

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Section: Mechanisms Of α-Defensin Bactericidal Actionmentioning

confidence: 99%

Section: α-Defensin Distribution and Gene Expressionmentioning

confidence: 99%

Section: Mouse α-Defensin Genomicsmentioning

confidence: 99%

Section: Mouse α-Defensin Genomicsmentioning

confidence: 99%

Section: Mouse α-Defensin Genomicsmentioning

confidence: 99%

See 3 more Smart Citations

Paneth cell α-defensins in enteric innate immunity

Ouellette

2011

Cell. Mol. Life Sci.

135

138

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SAMP1/YitFc mouse strain: A spontaneous model of Crohnʼs disease-like ileitis

Pizarro

Pastorelli

Bamias³

et al. 2011

Inflammatory Bowel Diseases

160

150

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The SAMP1/YitFc mouse strain represents a model of Crohn's disease (CD)-like ileitis that is ideal for investigating the pathogenesis of chronic intestinal inflammation. Differently from the vast majority of animal models of colitis, the ileal-specific phenotype characteristic of SAMP1/ YitFc mice occurs spontaneously, without genetic, chemical or immunological manipulation. In addition, SAMP1/YitFc mice possess remarkable similarities to the human condition in regard to disease location, histologic features, incidence of extra-intestinal manifestations, and response to conventional therapies. SAMP1/YitFc mice also display a well-defined time course of a predisease state, and phases of acute and chronic ileitis. As such, the SAMP1/YitFc model is particularly suitable for elucidating pathways that precede the clinical phenotype that may lead to preventive, and therefore more efficacious, intervention with the natural course of disease, or alternatively, for the development of therapeutic strategies directed against chronic, established ileitis. In the following review, we summarize important contributions made by our group and others that uncover potential mechanisms in the pathogenesis of CD using this unique murine model of chronic intestinal inflammation.

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The Immune System in IBD: Antimicrobial Peptides

Bevins

2017

Crohn's Disease and Ulcerative Colitis

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Elevated Expression of Paneth Cell CRS4C in Ileitis-prone SAMP1/YitFc Mice

Cited by 18 publications

References 69 publications

Paneth cell α-defensins in enteric innate immunity

Paneth cell α-defensins in enteric innate immunity

SAMP1/YitFc mouse strain: A spontaneous model of Crohnʼs disease-like ileitis

The Immune System in IBD: Antimicrobial Peptides

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