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https://www.readbyqxmd.com/read/28330897/rip2-is-required-for-nod2-mediated-lysozyme-sorting-in-paneth-cells
#1
Haifang Wang, Xinwen Zhang, Zhanguang Zuo, Qin Zhang, Ying Pan, Benhua Zeng, Wenxia Li, Hong Wei, Zhihua Liu
Paneth cells play an important role in maintaining intestinal homeostasis by secreting a large number of antimicrobial peptides into the intestinal lumen. In this study, we found that Rip2 is required for lysozyme sorting in Paneth cells in a manner that is dependent on Nod2, LRRK2, and Rab2a. Rip2 deficiency in mouse led to lysosomal degradation of lysozyme in Paneth cells and prevented the recruitment of Rab2a onto dense core vesicles (DCVs). Like Nod2 and LRRK2, Rip2 localizes to DCVs in Paneth cells, and its DCV localization depends on Nod2 and LRRK2...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28323883/ubiquitously-expressed-human-beta-defensin-1-hbd1-forms-bacteria-entrapping-nets-in-a-redox-dependent-mode-of-action
#2
Judith Raschig, Daniela Mailänder-Sanchez, Anne Berscheid, Jürgen Berger, Adam A Strömstedt, Lioba F Courth, Nisar P Malek, Heike Brötz-Oesterhelt, Jan Wehkamp
Ever since the discovery of endogenous host defense antimicrobial peptides it has been discussed how these evolutionary conserved molecules avoid to induce resistance and to remain effective. An Human ß-defensin 1 (hBD1) is an ubiquitously expressed endogenous antimicrobial peptide that exhibits qualitatively distinct activities between its oxidized and reduced forms. Here, we explore these antimicrobial mechanisms. Surprisingly, using electron microscopy we detected a so far unknown net-like structure surrounding bacteria, which were treated with the reduced but not the oxidized form of hBD1...
March 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28316379/high-fat-diet-alters-gut-microbiota-and-the-expression-of-paneth-cell-antimicrobial-peptides-preceding-changes-of-circulating-inflammatory-cytokines
#3
Xiulan Guo, Jinchao Li, Renyong Tang, Guodong Zhang, Huawei Zeng, Richard J Wood, Zhenhua Liu
Obesity is an established risk factor for many diseases including intestinal cancer. One of the responsible mechanisms is the chronic inflammation driven by obesity. However, it remains to be defined whether diet-induced obesity exacerbates the intestinal inflammatory status by cytokines produced in adipose tissue or the high fat diet first alters the gut microbiota and then drives intestinal inflammation. To address this question, we fed C57BL/6 mice with a high fat diet (HF, 60%) and sacrificed them sequentially after 8, 12, and 16 weeks, and then compositions of gut microbiota and expressions of antimicrobial peptides were determined...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28304405/the-erbb3-receptor-tyrosine-kinase-negatively-regulates-paneth-cells-by-pi3k-dependent-suppression-of-atoh1
#4
Dana Almohazey, Yuan-Hung Lo, Claire V Vossler, Alan J Simmons, Jonathan J Hsieh, Edie B Bucar, Michael A Schumacher, Kathryn E Hamilton, Ken S Lau, Noah F Shroyer, Mark R Frey
Paneth cells (PCs), a secretory population located at the base of the intestinal crypt, support the intestinal stem cells (ISC) with growth factors and participate in innate immunity by releasing antimicrobial peptides, including lysozyme and defensins. PC dysfunction is associated with disorders such as Crohn's disease and necrotizing enterocolitis, but the specific pathways regulating PC development and function are not fully understood. Here we tested the role of the neuregulin receptor ErbB3 in control of PC differentiation and the ISC niche...
March 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28303901/mutual-reinforcement-between-telomere-capping-and-canonical-wnt-signalling-in-the-intestinal-stem-cell-niche
#5
Ting-Lin B Yang, Qijun Chen, Jennifer T Deng, Geetha Jagannathan, John W Tobias, David C Schultz, Shan Wang, Christopher J Lengner, Anil K Rustgi, John P Lynch, F Brad Johnson
Critical telomere shortening (for example, secondary to partial telomerase deficiency in the rare disease dyskeratosis congenita) causes tissue pathology, but underlying mechanisms are not fully understood. Mice lacking telomerase (for example, mTR(-/-) telomerase RNA template mutants) provide a model for investigating pathogenesis. In such mice, after several generations of telomerase deficiency telomeres shorten to the point of uncapping, causing defects most pronounced in high-turnover tissues including intestinal epithelium...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28299479/l-glutamine-and-l-arginine-protect-against-enterotoxigenic-escherichia-coli-infection-via-intestinal-innate-immunity-in-mice
#6
Gang Liu, Wenkai Ren, Jun Fang, Chien-An Andy Hu, Guiping Guan, Naif Abdullah Al-Dhabi, Jie Yin, Veeramuthu Duraipandiyan, Shuai Chen, Yuanyi Peng, Yulong Yin
Dietary glutamine (Gln) or arginine (Arg) supplementation is beneficial for intestinal health; however, whether Gln or Arg may confer protection against Enterotoxigenic Escherichia coli (ETEC) infection is not known. To address this, we used an ETEC-infected murine model to investigate the protective effects of Gln and Arg. Experimentally, we pre-treated mice with designed diet of Gln or Arg supplementation prior to the oral ETEC infection and then assessed mouse mortality and intestinal bacterial burden. We also determined the markers of intestinal innate immunity in treated mice, including secretory IgA response (SIgA), mucins from goblet cells, as well as antimicrobial peptides from Paneth cells...
March 15, 2017: Amino Acids
https://www.readbyqxmd.com/read/28297666/canonical-wnt-signaling-ameliorates-aging-of-intestinal-stem-cells
#7
Kodandaramireddy Nalapareddy, Kalpana J Nattamai, Rupali S Kumar, Rebekah Karns, Kathryn A Wikenheiser-Brokamp, Leesa L Sampson, Maxime M Mahe, Nambirajan Sundaram, Mary-Beth Yacyshyn, Bruce Yacyshyn, Michael A Helmrath, Yi Zheng, Hartmut Geiger
Although intestinal homeostasis is maintained by intestinal stem cells (ISCs), regeneration is impaired upon aging. Here, we first uncover changes in intestinal architecture, cell number, and cell composition upon aging. Second, we identify a decline in the regenerative capacity of ISCs upon aging because of a decline in canonical Wnt signaling in ISCs. Changes in expression of Wnts are found in stem cells themselves and in their niche, including Paneth cells and mesenchyme. Third, reactivating canonical Wnt signaling enhances the function of both murine and human ISCs and, thus, ameliorates aging-associated phenotypes of ISCs in an organoid assay...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28296676/histopathologic-features-of-colitis-due-to-immunotherapy-with-anti-pd-1-antibodies
#8
Jonathan H Chen, Maryam K Pezhouh, Gregory Y Lauwers, Ricard Masia
Programmed cell death protein 1 (PD-1) blocking agents are novel immunotherapeutics used for treatment of advanced-stage malignancies. They have shown promise in the treatment of several malignancies, with greater efficacy and better tolerability than cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking agents. However, as with anti-CTLA-4 agents, clinically significant colitis remains an important complication. Although there is growing awareness of the histopathologic features of anti-CTLA-4 therapy, there is little information on the pathologic features of anti-PD-1 colitis...
March 14, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28296382/human-%C3%AE-defensin-6-a-small-peptide-that-self-assembles-and-protects-the-host-by-entangling-microbes
#9
Phoom Chairatana, Elizabeth M Nolan
Human α-defensin 6 (HD6) is a 32-residue cysteine-rich peptide that contributes to innate immunity by protecting the host at mucosal sites. This peptide is produced in small intestinal Paneth cells, stored as an 81-residue precursor peptide named proHD6 in granules, and released into the lumen. One unusual feature of HD6 is that it lacks the broad-spectrum antimicrobial activity observed for other human α-defensins, including the Paneth cell peptide human α-defensin 5 (HD5). HD6 exhibits unprecedented self-assembly properties, which confer an unusual host-defense function...
March 15, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28275690/intestinal-epithelial-specific-mtorc1-activation-enhances-intestinal-adaptation-after-small-bowel-resection
#10
Lauren Barron, Raphael C Sun, Bola Aladegbami, Christopher R Erwin, Brad W Warner, Jun Guo
BACKGROUND & AIMS: Intestinal adaptation is a compensatory response to the massive loss of small intestine after surgical resection. We investigated the role of intestinal epithelial cell-specific mammalian target of rapamycin complex 1 (i-mTORC1) in intestinal adaptation after massive small bowel resection (SBR). METHODS: We performed 50% proximal SBR on mice to study adaptation. To manipulate i-mTORC1 activity, Villin-Cre(ER) transgenic mice were crossed with tuberous sclerosis complex (TSC)1(flox/flox) or Raptor(flox/flox) mice to inducibly activate or inactivate i-mTORC1 activity with tamoxifen...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28273069/interplay-between-metabolic-identities-in-the-intestinal-crypt-supports-stem-cell-function
#11
Maria J Rodríguez-Colman, Matthias Schewe, Maaike Meerlo, Edwin Stigter, Johan Gerrits, Mia Pras-Raves, Andrea Sacchetti, Marten Hornsveld, Koen C Oost, Hugo J Snippert, Nanda Verhoeven-Duif, Riccardo Fodde, Boudewijn M T Burgering
The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5(+) crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt. Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5(+) CBCs and Paneth cells from the mouse small intestine display different metabolic programs...
March 8, 2017: Nature
https://www.readbyqxmd.com/read/28236968/regulation-of-embryonic-and-postnatal-development-by-the-csf-1-receptor
#12
Violeta Chitu, E Richard Stanley
Macrophages are found in all tissues and regulate tissue morphogenesis during development through trophic and scavenger functions. The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) is the major regulator of tissue macrophage development and maintenance. In combination with receptor activator of nuclear factor κB (RANK), the CSF-1R also regulates the differentiation of the bone-resorbing osteoclast and controls bone remodeling during embryonic and early postnatal development. CSF-1R-regulated macrophages play trophic and remodeling roles in development...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28219240/ratiometric-imaging-of-tissue-by-two-photon-microscopy-observation-of-a-high-level-of-formaldehyde-around-mouse-intestinal-crypts
#13
Subhankar Singha, Yong Woong Jun, Juryang Bae, Kyo Han Ahn
Ratiometric imaging by two-photon microscopy can offer a viable tool for the relative quantification of biological analytes inside tissue with minimal influence from environmental factors that affect fluorescence signal. We demonstrate the ratiometric imaging of formaldehyde at the suborgan level using a two-photon fluorescent probe, which involves pixel-to-pixel ratiometric data transformation. This study reveals for the first time a high level of formaldehyde around the crypts of mouse small intestine, implicating its possible protective role along with the released antimicrobials from the Paneth cells...
March 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28193209/secretion-of-biologically-active-pancreatitis-associated-protein-i-pap-by-genetically-modified-dairy-lactococcus-lactis-nz9000-in-the-prevention-of-intestinal-mucositis
#14
Rodrigo D Carvalho, Natalia Breyner, Zelia Menezes-Garcia, Nubia M Rodrigues, Luisa Lemos, Tatiane U Maioli, Danielle da Gloria Souza, Denise Carmona, Ana M C de Faria, Philippe Langella, Jean-Marc Chatel, Luis G Bermúdez-Humarán, Henrique C P Figueiredo, Vasco Azevedo, Marcela S de Azevedo
BACKGROUND: Mucositis is one of the most relevant gastrointestinal inflammatory conditions in humans, generated by the use of chemotherapy drugs, such as 5-fluoracil (5-FU). 5-FU-induced mucositis affects 80% of patients undergoing oncological treatment causing mucosal gut dysfunctions and great discomfort. As current therapy drugs presents limitations in alleviating mucositis symptoms, alternative strategies are being pursued. Recent studies have shown that the antimicrobial pancreatitis-associated protein (PAP) has a protective role in intestinal inflammatory processes...
February 13, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28174748/requirement-of-g%C3%AE-q-g%C3%AE-11-signaling-in-the-preservation-of-mouse-intestinal-epithelial-homeostasis
#15
Noboru Watanabe, Hirosato Mashima, Kouichi Miura, Takashi Goto, Makoto Yoshida, Akiteru Goto, Hirohide Ohnishi
BACKGROUND & AIMS: Proliferation, differentiation, and morphogenesis of the intestinal epithelium are tightly regulated by a number of molecular pathways. Coordinated action of intestine is achieved by gastrointestinal hormones, most of which exert these actions through G-protein-coupled receptors. We herein investigated the role of Gαq/11-mediated signaling in intestinal homeostasis. METHODS: Intestinal tissues from control (Gnaq(flox/flox)Gna11(+/+) ), Int-Gq knock-out (KO) (VilCre(+/-)Gnaq(flox/flox)Gna11(+/+) ), G11 KO (Gnaq(flox/flox)Gna11(-/-) ), and Int-Gq/G11 double knock-out (DKO) (VilCre(+/-)Gnaq(flox/flox)Gna11(-/-) ) mice were examined by microscopy, transmission electron microscopy, and immunohistochemistry...
November 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28174744/intestinal-gpcrs-control-paneth-cell-maturation-and-susceptibility-to-experimental-colitis
#16
EDITORIAL
Xiao Zhang, Nan Gao
No abstract text is available yet for this article.
November 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28174721/znt2-mediated-zinc-import-into-paneth-cell-granules-is-necessary-for-coordinated-secretion-and-paneth-cell-function%C3%A2-in%C3%A2-mice
#17
Abigail B Podany, Justin Wright, Regina Lamendella, David I Soybel, Shannon L Kelleher
BACKGROUND & AIMS: Defects in Paneth cell (PC) function are associated with microbial dysbiosis and intestinal inflammation. PC granules contain antimicrobial peptides, cytokines, and substantial stores of zinc (Zn). We hypothesized that Zn, transported into the granule through the Zn transporter (ZnT)2, is critical for signature PC functions. METHODS: ZnT2 was localized to PC granules using immunofluorescence and sucrose gradient fractionation in wild-type (wt) mice, and consequences of ZnT2 loss were characterized in ZnT2 knockout (ZnT2ko) mice...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28174718/the-paneth-cell-a-guardian-of-gut-health
#18
EDITORIAL
Mark Manary
No abstract text is available yet for this article.
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28147355/improvement-of-a-leaky-intestinal-barrier
#19
REVIEW
Eduard F Stange
In Crohn's disease, the mucus layer appears to be defective in terms of low defensin levels and lack of antibacterial activity. These deficiencies actually explain the Montreal phenotypes and the stable localization of disease in the terminal ileum with low α-defensins from Paneth cells and/or low β-defensins in colonic disease, respectively. Conversely, in ulcerative colitis (UC) the defensin production is normal or even induced, but the mucus layer is thinner and patchy, more in the liquid form and also chemically altered so that antibacterial peptides are not retained and lost into the luminal bacterial bulk...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28130498/myeloid-atg16l1-facilitates-host-bacteria-interactions-in-maintaining-intestinal-homeostasis
#20
Hong Zhang, Libo Zheng, Dermot P B McGovern, Ariel M Hamill, Ryan Ichikawa, Yoshitake Kanazawa, Justin Luu, Kotaro Kumagai, Marianne Cilluffo, Masayuki Fukata, Stephan R Targan, David M Underhill, Xiaolan Zhang, David Q Shih
Intact ATG16L1 plays an essential role in Paneth cell function and intestinal homeostasis. However, the functional consequences of ATG16L1 deficiency in myeloid cells, particularly macrophages, are not fully characterized. We generated mice with Atg16l1 deficiency in myeloid and dendritic cells and showed that mice with myeloid Atg16l1 deficiency had exacerbated colitis in two acute and one chronic model of colitis with increased proinflammatory to anti-inflammatory macrophage ratios, production of proinflammatory cytokines, and numbers of IgA-coated intestinal microbes...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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