Dataset Information

Peptide localization and gene structure of cryptdin 4, a differentially expressed mouse paneth cell alpha-defensin.

ABSTRACT: Paneth cells in crypts of the small intestine express antimicrobial peptides, including alpha-defensins, termed cryptdins in mice. Of the known Paneth cell alpha-defensins, the cryptdin 4 gene is unique, because it is inactive in the duodenum and expressed at maximal levels in the distal small bowel (D. Darmoul and A. J. Ouellette, Am. J. Physiol. 271:G68-G74, 1996). With a cryptdin 4-specific antibody, immunohistochemical staining of ileal Paneth cells was strong and specific for cytoplasmic granules, demonstrating that this microbicidal peptide is a secretory product of Paneth cells in the distal small intestine. Consistent with the pattern of cryptdin 4 mRNA distribution along the length of the gut, the cryptdin 4 peptide was not detected in duodenum. Structurally, the cryptdin 4 gene resembles other Paneth cell alpha-defensin genes. Its two exons, transcriptional start site, intron, splice sites, and 3' flanking sequences are characteristic of the highly conserved mouse alpha-defensin genes. However, in the region upstream of the transcriptional initiation site, the cryptdin 4 gene contains a repeated 130-bp element that is unique to this alpha-defensin gene. Every independent cryptdin 4 genomic clone examined carries the repeated element, which contains putative recognition sequences for TF-IID-EIIA, cMyc-RS-1, and IgHC.2/CuE1.1; the repeat proximal to the start of transcription replaces DNA at the corresponding position in other mouse alpha-defensin genes. We speculate that this unique duplicated element may have a cis-acting regulatory role in the positional specificity of cryptdin 4 gene expression.

SUBMITTER: Ouellette AJ

PROVIDER: S-EPMC97078 | biostudies-literature | 1999 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Peptide localization and gene structure of cryptdin 4, a differentially expressed mouse paneth cell alpha-defensin.

Ouellette A J AJ Darmoul D D Tran D D Huttner K M KM Yuan J J Selsted M E ME

Infection and immunity 19991201 12

Paneth cells in crypts of the small intestine express antimicrobial peptides, including alpha-defensins, termed cryptdins in mice. Of the known Paneth cell alpha-defensins, the cryptdin 4 gene is unique, because it is inactive in the duodenum and expressed at maximal levels in the distal small bowel (D. Darmoul and A. J. Ouellette, Am. J. Physiol. 271:G68-G74, 1996). With a cryptdin 4-specific antibody, immunohistochemical staining of ileal Paneth cells was strong and specific for cytoplasmic gr ...[more]

PMID: 10569786

Similar Datasets

Project description:IntroductionThe mechanism underlying radiation-induced gut microbiota dysbiosis is undefined. This study examined the effect of radiation on the intestinal Paneth cell α-defensin expression and its impact on microbiota composition and mucosal tissue injury and evaluated the radio-mitigative effect of human α-defensin 5 (HD5).MethodsAdult mice were subjected to total body irradiation, and Paneth cell α-defensin expression was evaluated by measuring α-defensin mRNA by RT-PCR and α-defensin peptide levels by mass spectrometry. Vascular-to-luminal flux of FITC-inulin was measured to evaluate intestinal mucosal permeability and endotoxemia by measuring plasma lipopolysaccharide. HD5 was administered in a liquid diet 24 hours before or after irradiation. Gut microbiota was analyzed by 16S rRNA sequencing. Intestinal epithelial junctions were analyzed by immunofluorescence confocal microscopy and mucosal inflammatory response by cytokine expression. Systemic inflammation was evaluated by measuring plasma cytokine levels.ResultsIonizing radiation reduced the Paneth cell α-defensin expression and depleted α-defensin peptides in the intestinal lumen. α-Defensin down-regulation was associated with the time-dependent alteration of gut microbiota composition, increased gut permeability, and endotoxemia. Administration of human α-defensin 5 (HD5) in the diet 24 hours before irradiation (prophylactic) significantly blocked radiation-induced gut microbiota dysbiosis, disruption of intestinal epithelial tight junction and adherens junction, mucosal barrier dysfunction, and mucosal inflammatory response. HD5, administered 24 hours after irradiation (treatment), reversed radiation-induced microbiota dysbiosis, tight junction and adherens junction disruption, and barrier dysfunction. Furthermore, HD5 treatment also prevents and reverses radiation-induced endotoxemia and systemic inflammation.ConclusionThese data demonstrate that radiation induces Paneth cell dysfunction in the intestine, and HD5 feeding prevents and mitigates radiation-induced intestinal mucosal injury, endotoxemia, and systemic inflammation.

Dataset Information

Peptide localization and gene structure of cryptdin 4, a differentially expressed mouse paneth cell alpha-defensin.

Publications

Peptide localization and gene structure of cryptdin 4, a differentially expressed mouse paneth cell alpha-defensin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets